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ABSTRACT Introduction The determinants of time to return to activity (RTA) and return to work (RTW) after carpal tunnel release (CTR) remain unclear. Methods We performed a systematic review of studies published from January 2000 to November 2022 involving patients treated with open (OCTR), mini-open (mOCTR), or endoscopic (ECTR) CTR and reporting RTA or RTW. The time to RTA and RTW were estimated using a random-effects meta-analysis model. Subgroup analysis and multivariable meta-regression explored sources of heterogeneity in outcomes. Results A total of 7386 patients in 48 studies (63 groups) were included, with 24 groups (4541 patients) treated with OCTR, 16 groups (1085 patients) treated with mOCTR, and 23 groups (1760 patients) treated with ECTR. Among 15 studies (20 groups) reporting RTA, the mean was 13.1 days (95% CI, 9.9–16.3; I2>99%). Shorter duration of postoperative activity restriction guidance was associated with faster RTA. Among 43 studies (58 groups) reporting RTW, the mean was 23.4 days (95% CI, 21.4–25.3; I2>99%). Procedure type (mOCTR and ECTR compared to OCTR), prospective study design, and smaller proportion of patients receiving disability benefit were associated with faster RTW. Conclusions The time to RTA and RTW after CTR are highly variable and influenced by study-, patient-, and physician-specific factors.