Background Endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) both have advantages and disadvantages for the treatment of carpal tunnel syndrome (CTS). We compared the effectiveness and safety of ECTR and OCTR based on evidence from a high-level randomized controlled trial. Methods We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Medline to identify relevant articles published until August 2022. Data regarding operative time, grip strength, Boston Carpal Tunnel Questionnaire scores, digital sensation, patient satisfaction, key pinch strength, return to work time, and complications were extracted and compared. All mean differences (MD) and odds ratios (OR) were expressed as ECTR relative to OCTR.