Blood flow restriction (BFR) in combination with exercise has been shown to result in favorable effects on skeletal muscle mass and function. However, most protocols have used an arbitrary pressure or they have based the restrictive pressure off of brachial systolic blood pressure, which is not a valid predictor of arterial occlusion in the lower body. This study sought to determine the most effective low load protocol with and without different degrees of BFR (determined based on limb circumference) and determine how it compares to higher load (HL) resistance exercise. PURPOSE: The purpose of this study was to compare acute skeletal muscle changes following differing resistance exercise protocols. In addition, the perceptual response to each of those protocols was investigated. METHODS: Participants completed five separate visits. On the first visit, participants: 1) completed paperwork; 2) were screened further for eligibility (Blood Pressure; BMI); 3) completed one repetition maximum testing on the knee extension; and 4) were familiarized with the BFR stimulus. Following the first visit, participants were randomly assigned to either group A, group B, or group C. Within each group, the participants were further randomized into which condition they completed first, second, third, and fourth. The conditions included three exercise conditions and one control condition. During each visit, participants had their muscle thickness and circumferences measured on their non-dominant leg. Following this, their dominant leg was prepped for electromyography (EMG). Participants completed a maximal voluntary contraction (MVC) with their dominant leg, rested for five minutes, and then completed the protocol designated for that day. The protocols within Group A included HL exercise at 70% 1RM, exercise at 20% 1RM with 40% estimated arterial occlusion (20%/40 BFR), exercise at 30% 1RM with 40% estimated arterial occlusion (30%/40 BFR), and a non-exercise control (CON). The protocols within Group B included exercise to failure at 30% 1RM, exercise at 20% 1RM with 50% estimated arterial occlusion (20%/50 BFR), exercise at 30% 1RM with 50% estimated arterial occlusion (30%/50 BFR), and a non-exercise CON. The protocols within Group C included exercise to failure at 20% 1RM, exercise at 20% 1RM with 60% estimated arterial occlusion (20%/60 BFR), exercise at 30% 1RM with 60% estimated arterial occlusion (30%/60 BFR), and a non-exercise CON. The 70% 1RM protocol was completed with one minute rest between sets. All other protocols were separated by 30s rest. In addition, after every set of exercise, RPE and discomfort were quantified. During the CON conditions, participants sat in the knee extension device for ~5.5 minutes to mimic the estimated time to complete a normal exercise bout. A comparison across groups was plotted and visually examined to descriptively compare conditions when effect sizes were unable to be calculated (i.e. EMG, perceptual responses). RESULTS: Forty-five physically active males passed initial screening and gave informed consent to participate in the study. Of those initial 45 participants, only 40 completed all of the testing sessions. Within the BFR conditions, increasing the load from 20% to 30% 1RM significantly increased the exercise volume, regardless of the pressure applied. Although not examined statistically, plotting the exercise volumes together (i.e. across groups) suggests that the 20% to failure condition results in the greatest volume lifted, followed by 30% to failure and HL conditions, which had similar volumes. The decrease in torque was statistically similar between the exercise conditions within each group, except for the 20%/40 BFR condition whose decrease did not exceed the error of the measurement. When examining the magnitude of the change across groups for each load, the effect sizes were slightly higher in the 30% 1RM BFR conditions compared to the 20% 1RM BFR conditions. In addition, increasing the applied pressure from 40% BFR to 50% BFR increased the magnitude of the effect; however, increasing the pressure up to 60% BFR reduced the effect size in the 30% 1RM BFR conditions. For non-BFR conditions, the effect sizes were similar, but with 20% to failure having the largest effect. With respect to muscle cell swelling, the acute changes in muscle size appeared fairly similar across all exercise conditions within each group regardless of load and pressure. The increase in lactate was similar between the exercise conditions within each group, except for the 20% 1RM BFR conditions, whose increases were always significantly less than those of the other exercise conditions. When examining the magnitude of the change across groups for each load, the effect sizes were higher in the 30% 1RM BFR conditions compared to the 20% 1RM BFR conditions. Increasing the applied pressure from 40% BFR to 50% BFR increased the magnitude of the effect; however, increasing the applied pressure up to 60% BFR reduced the effect size. For the non-BFR conditions, the effect sizes were highest in the HL and 30% to failure conditions, with 20% to failure having the smallest effect. The increase in concentric EMG amplitude was augmented when the load was increased from 20%1RM to 30% 1RM within each group. In addition, the 30%/50 BFR conditions concentric EMG amplitude was statistically similar to the 30% to failure condition. Increasing the applied pressure from 40% BFR to 50% BFR increased concentric EMG amplitude independent of load; however, increasing the applied pressure up to 60% BFR did not appear to augment the response. The HL condition had the highest concentric amplitudes throughout. The increase in eccentric EMG amplitude was augmented when the load was increased from 20%1RM to 30% 1RM within each group except for Group C. In Group C, there was no difference between 20%/60 BFR and 30%/60 BFR for eccentric EMG amplitude of the last three repetitions. In addition, the 30%/50 BFR conditions eccentric EMG amplitude was statistically similar to the 30% to failure condition. Increasing the applied pressure from 40% BFR to 50% BFR increased concentric EMG amplitude independent of load; however, increasing the applied pressure up to 60% BFR did not appear to augment the response. The HL condition had the highest eccentric amplitudes throughout. Concentric EMG mean power frequency increased from set 1 to set 3 within Group A for the last three repetitions, but no differences were observed at any time point within Group B or Group C. Increasing the pressure or the load did not appear to change concentric mean power frequency. Eccentric EMG mean power frequency of the first three repetitions decreased from set 1 to set 2, set 3, and set 4 for each condition within each group. For the last three repetitions, there were differential responses within each group. Increasing the pressure or the load did not appear to change eccentric mean power frequency. The ratings of perceived exertion (RPE) increased within each group. In Group A, 20%/40 BFR had the lowest overall RPE while 30%/40 BFR and HL training had ratings similar to each other. In Group B, 20%/50 BFR had the lowest overall RPE while 30%/50 BFR and 30% to failure were similar to each other. In Group C, there were minor differences in set 1, otherwise the ratings were similar throughout. When examining the change in RPE across groups for each load, the ratings were similar in the 20% 1RM BFR conditions compared to the 30% 1RM BFR conditions. In addition, increasing the applied pressure from 40% BFR to 50% BFR increased RPE at 20% 1RM; however, increasing the applied pressure up to 60% BFR did not lead to a higher RPE. With 30% 1RM, RPE did not appear different across pressures. For the non-BFR conditions, the HL condition had the lowest RPE, while the ratings were similar between 20% and 30% 1RM to failure. The ratings of discomfort increased within each group. In Group A, the 20%/40 BFR had the lowest overall ratings of discomfort while the 30%/40 BFR condition had the highest. Neither group differed from the HL condition, except for set 3 where the 30%/40 BFR condition had higher ratings. In Groups B C, ratings of discomfort were similar throughout except for set 1 in Group B. When examining the change in discomfort across groups for each load, the ratings were lower in the 20% 1RM BFR conditions compared to the 30% 1RM BFR conditions. In addition, increasing the applied pressure from 40% BFR to 50% BFR increased ratings of discomfort at 20% 1RM, and there was a further increase in the rating when the applied pressure was increased to 60% BFR. For 30% 1RM, the ratings of discomfort descriptively differed across each set. In set 1, the ratings of discomfort were highest for 40% BFR and lowest with 60% BFR. In set 2, the ratings of discomfort were similar across conditions. For sets 3 and 4, the ratings of discomfort were higher with 40 and 60% BFR and lower with 50% BFR. For the non-BFR conditions, the HL condition had the lowest ratings of discomfort, while the ratings were highest with the 20% 1RM to failure condition. CONCLUSIONS: This study found that knee extension exercise at 30% 1RM in combination with BFR at an estimated arterial occlusion pressure of 50% resulted in changes similar to those seen with HL exercise. In addition, 30% 1RM to failure also produced changes similar to HL exercise, albeit at a higher exercise volume. However, it is noted that the EMG amplitude of the lower loads never reached that observed with HL exercise. Since similar changes have been observed previously in chronic training studies, these findings suggest that other mechanisms may be playing a more prominent role with lower loads.