Kassiano, W, Costa, B, Nunes, JP, Ribeiro, AS, Schoenfeld, BJ, and Cyrino, ES. Which ROMs lead to Rome? a systematic review of the effects of range of motion on muscle hypertrophy. J Strength Cond Res 37(5): 1135–1144, 2022—Resistance exercise range of motion (ROM) influences muscular adaptations. However, there are no consistent practical guidelines about the optimal ROM for maximizing muscle hypertrophy. The objective of this article was to systematically review the literature for studies that compared the effects of full ROM (fROM) and partial ROM (pROM) on muscle hypertrophy. PubMed/MEDLINE, Scopus, and Web of Science databases were searched to identify articles from the earliest record up to and including April 2022. We calculated the effect size (ES) scores of the variables of interest. Eleven studies were included in the review. Full ROM and pROM performed in the initial part of the ROM elicited greater muscle hypertrophy of the rectus femoris, vastus lateralis, biceps brachii, and brachialis distal sites (between-groups ES: 0.20–0.90) than pROM performed in the final part of the ROM. fROM elicited greater muscle growth on the gluteus maximus and adductors than pROM in the final part of the ROM (between-groups ES: 0.24–0.25). Initial pROM produced more favorable proximal rectus femoris hypertrophy than fROM (between-groups ES: 0.35–0.38). pROM in the middle part of the ROM elicited greater triceps brachii hypertrophy than fROM (between-group ES: 1.21). In conclusion, evidence suggests that when training at a longer muscle length—through either pROM or fROM—some muscles, such as quadriceps femoris, biceps brachii, and triceps brachii, tend to experience optimal growth. Thus, the use pROM in the initial part of the excursion in combination with fROM training should be considered when prescribing hypertrophy-oriented resistance training programs.