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Producción Científica, Aim of the study Systematic review and meta-analysis to assess the effectiveness of manual therapy in improving carpal tunnel syndrome (CTS) symptoms, physical function, and nerve conduction studies. Method MEDLINE, Web of Science, SCOPUS, Cochrane Library, TRIP database, and PEDro databases were searched from the inception to September 2021. PICO search strategy was used to identify randomized controlled trials applying manual therapy on patients with CTS. Eligible studies and data extraction were conducted independently by two reviewers. Methodology quality and risk of bias were assessed by PEDro scale. Outcomes assessed were pain intensity, physical func- tion, and nerve conduction studies. Results Eighty-one potential studies were identified and six studies involving 401 patients were finally included. Pain inten- sity immediately after treatment showed a pooled standard mean difference (SMD) of − 2.13 with 95% confidence interval (CI) (− 2.39, − 1.86). Physical function with Boston Carpal Tunnel Syndrome Questionnaire (BCTS-Q) showed a pooled SMD of − 1.67 with 95% CI (− 1.92, − 1.43) on symptoms severity, and a SMD of − 0.89 with 95% CI (− 1.08, − 0.70) on functional status. Nerve conduction studies showed a SMD of− 0.19 with 95% CI (−0.40, − 0.02) on motor conduction and a SMD of − 1.15 with 95% CI (− 1.36, − 0.93) on sensory conduction. Conclusions This study highlights the effectiveness of manual therapy techniques based on soft tissue and neurodynamic mobilizations, in isolation, on pain, physical function, and nerve conduction studies in patients with CTS., Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE