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Objective People diagnosed with carpal tunnel syndrome (CTS) have fibrosis between the soft, connective, and neural tissues that could worsen the compression of the median nerve. The diacutaneous fibrolysis (DF) technique may release tissue adhesions and increase the mobility of connective tissues. The purpose of this study was to compare the outcomes of DF in people with mild to moderate CTS on mechanosensitivity, disability, and nerve conduction studies. Methods This was a secondary analysis of a double-blinded, randomized, placebo-controlled trial. Patients were recruited between April and September 2016 from the Department of Neurophysiology at the Hospital Miguel Servet, Zaragoza, Spain. Thirty-nine people (52 wrists) diagnosed with mild to moderate CTS were included. Participants were randomly assigned to either the DF group (n = 26) or the sham group (n = 26). Both groups received 5 therapy sessions, 2 sessions per week. Mechanosensitivity with the Upper Limb Neurodynamic Test 1, symptom severity and functional status with the Boston Carpal Tunnel Questionnaire, and median nerve sensory conduction velocity with nerve conduction studies were the outcomes measured. Assessments were recorded at baseline and after the intervention. Results The DF group showed significant improvements in the following: mechanosensitivity, with 28.46 degrees of elbow extension range of motion (95% CI = 19.2–37.7); an increase of 1.0 point (95% CI = 0.7–1.4) for the Boston Carpal Tunnel Questionnaire symptom severity and functional status score; and sensory conduction velocity of median nerve, which improved to 5.8 m/s (95% CI = 2.5–9.2). Conclusion Participants with mild to moderate CTS experienced improvements in symptom severity, functional status, mechanosensitivity, and nerve conduction studies after 5 sessions of DF. Impact This study provides evidence of an approach based on soft and connective tissues around the median nerve in patients with CTS. [ABSTRACT FROM AUTHOR]