Prehabilitation programs for patients undergoing orthopedic surgery have been gaining popularity in recent years. However, the current literature has produced varying results./r/nTo evaluate whether prehabilitation is associated with improved preoperative and postoperative outcomes compared with usual care for patients undergoing orthopedic surgery./r/nBibliographic databases (MEDLINE, CINAHL [Cumulative Index to Nursing and Allied Health Literature], AMED [Allied and Complementary Medicine], Embase, PEDRO [Physiotherapy Evidence Database], and Cochrane Central Register of Controlled Trials) were searched for published trials, and the Institute for Scientific Information Web of Science, System for Information on Grey Literature in Europe, and European clinical trials registry were searched for unpublished trials from January 1, 2000, to June 30, 2022./r/nRandomized clinical trials (RCTs) comparing prehabilitation with standard care for any orthopedic surgical procedure were included./r/nTwo independent reviewers screened trials. Data were pooled using a random-effects model. Recommendations were determined using the Grading of Recommendations Assessment, Development and Evaluation system and the study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline./r/nPain, function, muscle strength, and health-related quality of life (HRQOL)./r/nForty-eight unique trials involving 3570 unique participants (2196 women [61.5%]; mean [SD] age, 64.1 [9.1] years) were analyzed. Preoperatively, moderate-certainty evidence favoring prehabilitation was reported for patients undergoing total knee replacement (TKR) for function (standardized mean difference [SMD], -0.70 [95% CI, -1.08 to -0.32]) and muscle strength and flexion (SMD, 1.00 [95% CI, 0.23-1.77]) and for patients undergoing total hip replacement (THR) for HRQOL on the 36-item Short Form Health Survey (weighted mean difference [WMD], 7.35 [95% CI, 3.15-11.54]) and muscle strength and abduction (SMD, 1.03 [95% CI, 0.03-2.02]). High-certainty evidence was reported for patients undergoing lumbar surgery for back pain (WMD, -8.20 [95% CI, -8.85 to -7.55]) and moderate-certainty evidence for HRQOL (SMD, 0.46 [95% CI, 0.13-0.78]). Postoperatively, moderate-certainty evidence favoring prehabilitation was reported for function at 6 weeks in patients undergoing TKR (SMD, -0.51 [95% CI, -0.85 to -0.17]) and at 6 months in those undergoing lumbar surgery (SMD, -2.35 [95% CI, -3.92 to -0.79]). Other differences in outcomes favoring prehabilitation were of low to very low quality of evidence./r/nIn this systematic review and meta-analysis of RCTs, moderate-certainty evidence supported prehabilitation over usual care in improving preoperative function and strength in TKR and HRQOL and muscle strength in THR, high-certainty evidence in reducing back pain, and moderate-certainty evidence in improving HRQOL in lumbar surgery. Postoperatively, moderate-certainty evidence supported prehabilitation for function following TKR at 6 weeks and lumbar surgery at 6 months. Prehabilitation showed promising results for other outcomes, although high risk of bias and heterogeneity affected overall quality of evidence. Additional RCTs with a low risk of bias investigating preoperative and postoperative outcomes for all orthopedic surgical procedures are required.