OBJECTIVE: To investigate the effectiveness of exercise-based rehabilitation programs compared with nonexercise intervention or no intervention for people with hand osteoarthritis (OA). DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched 5 databases on July 23, 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared the effectiveness of rehabilitation programs that included an exercise component, with nonexercise intervention or no intervention for people with hand OA. DATA SYNTHESIS: Standardized mean differences (SMDs) were pooled using a random-effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: Fourteen trials were included in the meta-analysis (n = 1341 participants). In the immediate term (<24 weeks), there was low-certainty evidence of an effect of exercise-based rehabilitation on improving pain (13 trials; SMD = -0.65; 95% CI: -1.06, -0.25), function (11 trials; SMD = -0.35; 95% CI: -0.54, -0.15), and grip strength (14 trials; SMD = 0.21; 95% CI: 0.03, 0.38). There was moderate-certainty evidence of an effect on reducing stiffness (7 trials; SMD = -0.33; 95% CI: -0.51, -0.16). There was low-certainty evidence of no effect on improving pinch strength and quality of life. For the long term (≥24 weeks), there was low-certainty evidence that exercise-based rehabilitation had no additional effect on improving pain, function, and stiffness. CONCLUSION: Exercise-based rehabilitation improved pain, function, stiffness, and grip strength in people with hand OA in the immediate term; the benefits were not maintained in the long term. J Orthop Sports Phys Ther 2024;54(7):1-11. Epub 20 March 2024. doi:10.2519/jospt.2024.12241 .