A BSTRACT Background and Objective: Vitamin D accelerates myelin repair and recovery after nerve damage. This study aimed to evaluate the effect of vitamin D on the prognosis of patients with carpal tunnel syndrome (CTS). Methods: A randomized clinical trial was conducted in the orthopedic ward of Golestan and Imam Khomeini hospitals in Ahvaz for 2 years (from October 2018 to October 2020). Patients were divided into three groups: the first group received 1,000 units of vitamin D daily, the second group received 4,000 units of vitamin D per week for the first 4–6 weeks and then 2,000 units per month, and the third group received no vitamin D supplementation. The results were compared before and after 6 months between the study groups. Results: A total of 105 patients were included in the study, who were divided into three groups. The mean age of the patients was 39.24 ± 7.01 years (25–52 years). The mean level of the vitamin D in the control group was 25.40 ± 8.37 ng/mL, the group receiving 1,000 units/day was 26.71 ± 8.70 ng/mL, and the group receiving 50,000 units per week was 26.17 ± 8.63 ng/mL. The mean values of preoperative pain intensity, symptom severity, and functional status were almost the same in the three groups. These values were reduced after surgery in the two groups receiving the drug compared to the control group. Conclusions: The findings of the study showed that the administration of vitamin D supplementation in patients with CTS can significantly improve the postoperative symptoms of patients who underwent tendon release surgery and further improve the severity of symptoms and dysfunction of patients.