Refalo, MCHelms, ERTrexler, ETHamilton, DLFyfe, JJ2023-07-052023-07-052022-11-05Sports Medicine, ISSN: 0112-1642 (Print); 1179-2035 (Online), Springer Science and Business Media LLC, 53(3), 649-665. doi: 10.1007/s40279-022-01784-y0112-16421179-2035http://hdl.handle.net/10292/16373Background and Objective: This systematic review with meta-analysis investigated the influence of resistance training proximity-to-failure on muscle hypertrophy. Methods: Literature searches in the PubMed, SCOPUS and SPORTDiscus databases identified a total of 15 studies that measured muscle hypertrophy (in healthy adults of any age and resistance training experience) and compared resistance training performed to: (A) momentary muscular failure versus non-failure; (B) set failure (defined as anything other than momentary muscular failure) versus non-failure; or (C) different velocity loss thresholds. Results: There was a trivial advantage for resistance training performed to set failure versus non-failure for muscle hypertrophy in studies applying any definition of set failure [effect size=0.19 (95% confidence interval 0.00, 0.37), p=0.045], with no moderating effect of volume load (p=0.884) or relative load (p=0.525). Given the variability in set failure definitions applied across studies, sub-group analyses were conducted and found no advantage for either resistance training performed to momentary muscular failure versus non-failure for muscle hypertrophy [effect size=0.12 (95% confidence interval −0.13, 0.37), p=0.343], or for resistance training performed to high (>25%) versus moderate (20–25%) velocity loss thresholds [effect size=0.08 (95% confidence interval −0.16, 0.32), p=0.529]. Conclusion: Overall, our main findings suggest that (i) there is no evidence to support that resistance training performed to momentary muscular failure is superior to non-failure resistance training for muscle hypertrophy and (ii) higher velocity loss thresholds, and theoretically closer proximities-to-failure do not always elicit greater muscle hypertrophy. As such, these results provide evidence for a potential non-linear relationship between proximity-to-failure and muscle hypertrophy.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/4201 Allied Health and Rehabilitation Science42 Health Sciences4207 Sports Science and ExerciseMusculoskeletal0913 Mechanical Engineering1106 Human Movement and Sports Sciences1302 Curriculum and PedagogySport Sciences4201 Allied health and rehabilitation science4207 Sports science and exerciseHumansMuscle, SkeletalResistance TrainingMuscle StrengthHypertrophyMuscle, SkeletalHumansHypertrophyMuscle StrengthResistance TrainingHumansMuscle, SkeletalResistance TrainingMuscle StrengthHypertrophyJournal ArticleOpenAccess10.1007/s40279-022-01784-y