Low-load combined with blood flow restriction (BFR) resistance training has been reported to increase muscle size and muscle strength similar to traditional high-load resistance training. However, the mechanism of muscle hypertrophy induced by low-load resistance training with BFR is not clear. Additionally, the cardiovascular responses to low-load resistance training have not been elucidated. PURPOSE: To investigate the muscular (muscle thickness, arm circumference muscle activity and muscle strength) and cardiovascular (arterial stiffness and forearm blood flow) responses of eight weeks of low-load unilateral elbow flexor resistance training with BFR compared to traditional high-load resistance training, and to compare the acute skeletal muscle responses (muscle thickness, muscle activity, isometric strength, hematocrit and blood lactate) between traditional high-load and low-load with BFR unilateral elbow flexor resistance exercise in college-aged males. METHODS: Fourteen healthy college-aged males were randomly assigned to either the experimental group (n = 9) or control group (n = 5, CON) and each arm of the participants in the experimental group were randomly assigned to either the traditional high-load protocol (HI, 75% 1-RM and 3 sets of 10 reps) or low-load with BFR protocol (LI-BFR, 30% 1-RM and 30 reps following 3 sets of 15reps with 50% arterial occlusion pressure). The participants in the experimental group completed eight weeks of unilateral elbow flexor training (3 times per week). Both arms of participants in the CON group were assigned to the control protocol and the participants in the CON group maintained their daily physical activity and did not participate in any exercise sessions during the training period. All of the participants completed muscular and cardiovascular measurements two times before the training began (PRE 1 and PRE2) and once after the training ended (POST). Additionally, the participants in the experimental group completed the acute response testing during the first and second sessions of the fourth week of the training period and measurements were determined before and after an acute bout of HI or LI-BFR protocol in each session. The values at PRE1 and PRE 2 were averaged for further analysis. When there were no group differences at the baseline, ANOVA with post-hoc testing was utilized, and when significant group differences were detected at the baseline, ANCOVA with post-hoc testing was used to examine main effects (time and group) and interaction (time × group) effects. Alpha was set at p < 0.05. RESULTS: Muscle thickness and arm circumference at all sites in both HI and LI-BFR groups were significantly increased over time, but not in the CON group. 1-RM and isometric strength in both HI and LI-BFR groups were significantly increased over time, but not in the CON group, and the 1-RM in the HI group was significantly greater than the CON at the POST test. There were group differences at baseline for arterial stiffness (PWV) and forearm blood flow (FBF). PWV and FBF were unchanged over time when analyzed by ANCOVA. In the acute response testing, muscle thickness, arm circumference, muscle strength, muscle activity, blood lactate, and hematocrit values in both HI and LI-BFR groups showed similar responses. CONCLUSION: Both traditional high-load and low-load with BFR unilateral elbow flexor resistance training resulted in similar muscle hypertrophy and strength gains without any changes in cardiovascular function. In addition, acute cell swelling induced by a single bout of the LI-BFR protocol may represent the best explanation of a mechanism for BFR related muscle hypertrophy.