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Background: Numerous individual studies suggest that rest may have a negative effect on outcomes following concussion. Purpose: To perform a systematic meta-analysis of the effects of prescribed rest compared with active interventions after concussion. Study Design: Meta-analysis; Level of evidence, 4. Methods: A meta-analysis (using the Hedges g) of randomized controlled trials and cohort studies was conducted to evaluate the effects of prescribed rest on symptoms and recovery time after concussion. Subgroup analyses were performed for methodological, study, and sample characteristics. Data sources were obtained from systematic search of key terms using Ovid Medline, Embase, Cochrane Database of Systematic Reviews, APA PsycINFO, Web of Science, SPORTDiscus, and ProQuest dissertations and theses through May 28, 2021. Eligible studies were those that (1) assessed concussion or mild traumatic brain injury; (2) included symptoms or days to recovery for ≥2 time points; (3) included 2 groups with 1 group assigned to rest; and (4) were written in the English language. Results: In total, 19 studies involving 4239 participants met criteria. Prescribed rest had a significant negative effect on symptoms (k = 15; g = −0.27; SE = 0.11; 95% CI, −0.48 to −0.05; P =.04) but not on recovery time (k = 8; g = −0.16; SE = 0.21; 95% CI, −0.57 to 0.26; P =.03). Subgroup analyses suggested that studies with shorter duration (<28 days) (g = −0.46; k = 5), studies involving youth (g = −0.33; k = 12), and studies focused on sport-related concussion (g = −0.38; k = 8) reported higher effect sizes. Conclusion: The findings support a small negative effect for prescribed rest on symptoms after concussion. Younger age and sport-related mechanisms of injury were associated with a greater negative effect size. However, the lack of support for an effect for recovery time and the relatively small overall numbers of eligible studies highlight ongoing concerns regarding the quantity and rigor of clinical trials in concussion. Registration: CRD42021253060 (PROSPERO). [ABSTRACT FROM AUTHOR]