BACKGROUND: Low-load resistance training (< 50% of one-repetition maximum [1RM]) associated with blood-flow restriction (BFR-RT) has been thought to promote increases in muscle strength and mass. However, it remains unclear if the magnitude of these adaptations is similar to conventional high-load resistance training (> 65% 1RM; HL-RT). OBJECTIVE: To compare the effects of HL- versus BFR-RT on muscle adaptations using a systematic review and meta-analysis procedure. METHODS: Studies were identified via electronic databases based on the following inclusion criteria: (a) pre- and post-training assessment of muscular strength; (b) pre- and post-training assessment of muscle hypertrophy; (c) comparison of HL-RT vs. BFR-RT; (d) score ≥ 4 on PEDro scale; (e) means and standard deviations (or standard errors) are reported from absolute values or allow estimation from graphs. If this last criterion was not met, data were directly requested from the authors. RESULTS: The main results showed higher increases in muscle strength for HL- as compared with BFR-RT, even when considering test specificity, absolute occlusion pressure, cuff width, and occlusion pressure prescription. Regarding the hypertrophic response, results revealed similar effects between HL- and BFR-RT, regardless of the absolute occlusion pressure, cuff width, and occlusion pressure prescription. CONCLUSIONS: Based on the present data, maximum muscle strength may be optimized by specific training methods (i.e., HL-RT) while both HL- and BFR-RT seem equally effective in increasing muscle mass. Importantly, BFR-RT is a valid and effective approach for increasing muscle strength in a wide spectrum of ages and physical capacity, although it may seem particularly of interest for those individuals with physical limitations to engage in HL-RT.