[Objective] To compare the clinical efficacy of mini-open carpal tunnel release and traditional carpal tunnel release in the treatment of moderate and severe carpal tunnel syndrome(CTS). [Methods] Using prospective cohort study, we selected 118 patients with moderate to severe carpal tunnel syndrome admitted to our department from October 2017 to December 2019, and 62 patients underwent mini-open carpal tunnel release (mini-open group),56 patients underwent traditional open carpal tunnel release(traditional group).The operation time, length of incision, intraoperative blood loss, hospitalization time, preoperative and postoperative visual analogue (VAS) scale and Boston Carpal Tunnel Questionnaire(BCTQ) scores, the incidence of scar pain were compared between the two groups .Kelly's evaluation was used to evaluate the clinical efficacy. [Results] All the 118 cases were healed at first grade. The operation time, length of incision, intraoperative blood loss and hospitalization time of the mini-open group were significantly shorter than those of the traditional group (P < 0.01). VAS score and BCTQ symptom score of the mini-open group were lower than those of the traditional group at 1 and 3 months after surgery (P < 0.05), but there was no significant difference between the two groups at 6 and 12 months after surgery (P > 0.05). The BCTQ functional status scale of the mini-open group were lower than those of the traditional group at 3, 6 and 12 months after operation (P < 0.05). The incidence of scar pain 6 months and 12 months after surgery in the mini-open group was lower than that in the traditional group (P < 0.05). There was no significant difference in the excellent and good rate between the two groups at 6 months after surgery (P > 0.05), this rate of the mini-open group at 12 months after surgery was higher than that of the traditional group (P < 0.05). [Conclusion] Mini-open carpal tunnel release has the characteristics of small incision, short operation time and hospitalization time. Compared with traditional open carpal tunnel release, it can improve the early postoperative clinical symptoms of patients, and is conducive to the long-term functional recovery of patients after surgery and reduce the incidence of postoperative scar pain.