To evaluate the clinical effectiveness of wrist splint usage arranged by determining the optimal position on which the median nerve is compressed the least through sonographic examination for patients with carpal tunnel syndrome (CTS). This study was a prospective, clinical trial with a 6-week follow-up. Twenty-four patients diagnosed clinically and electromyographically with CTS were included in the study. A total of 37 wrists were studied on. When the patients were grouped according to the optimal position, Group I comprising 16 (43.24%) wrists was at 15 degree flexion, Group II comprising 12 (32.43%) wrists was neutral, Group III comprising 6 (16.22%) wrists was at 15° extension and Group IV comprising 3 (8.11%) wrists was at 30° extension configurations. Groups I, II and III were included in clinical follow-up. Symptom severity score (SSS), functional status score (FSS), Grip strength and Pinch strength were used for the clinical follow-up and evaluation of the patients. When pre- and post-treatment were compared, a statistically significant recovery was detected in all three groups in respect to SSS (Group I P < 0.01, Group II P < 0.05, Group III P < 0.05). A statistically significant recovery was detected for FSS only in Group I (P < 0.05) and for Grip strength in Group II (P < 0.05). When the groups were compared among themselves, no statistically significant difference was detected for any of the parameters (P > 0.05). In this study, by sonographic examination of the patients included in the study with CTS, we saw that the optimal position on which the median nerve is compressed the least varies depending on the individual and we determined that this position was 15° flexion most frequently for our patients. We also observed that in clinical follow-up of wrist splint usage arranged on custom optimal position results in significant recovery.