Background: Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. Moreover, carpal tunnel release (CTR) surgery generally has excellent results. The present study aimed to investigate the predictors of clinical outcomes and satisfaction in patients with CTR. Methods: In this observational prospective cohort study, 152 patients with open carpal tunnel release surgery were investigated. Complete clinical examinations were performed and recorded before the surgery, two weeks after the surgery and 6 months after the surgery. The Boston Carpal Tunnel Questionnaire (BCTQ) were assessed on admission and at last follow-up visits to evaluate clinical outcomes. Patients' satisfaction was determined by a 10-point verbal descriptor nominal scale (1 = very poor, 5 = fair and 10 = excellent) and recorded during the last follow-up visits. Results: Among 152 patients who were investigated, there were 118 (77.6%) females and 34 (22.36%) males. Overall, surgery improved the outcomes based on Symptom Severity Scale (SSS) and Functional Status Scale (FSS) (P < 0.05). Most of the considered variables did not show significant effects on clinical outcomes and patients' satisfaction. However, duration of symptoms and electrophysiological severity were the predictors of the change score in SSS(P < 0.05). As well as, age was the only predictor of the change score in FSS (P < 0.05). Finally, according to the linear regression model, the pre-operative grip strength and age were the independent predictors of post-operative satisfaction (P < 0.05). Conclusions: Results of the present study revealed that there was a significant improvement in clinical outcomes after CTS surgery. Stronger pre-operative grip strength and younger age were independent predictors of higher post-operative satisfaction. These results can be used in pre-operative counseling and management of post-operative expectations.