Objectives: There is no consensus on whether conservative treatment with night splints is indicated also in moderate and severe stages of carpal tunnel syndrome (CTS). The goal of this study was to compare the efficacy of night-time splinting at different stages of CTS. Material and Methods: Forty-five patients with electrodiagnostic (EDX) features of CTS included in the study were divided into 2 groups based on nerve conduction studies. The patients in the first group had only median nerve sensory fiber involvement, whereas the patients in the second group had also motor fiber involvement. The custom-made volar night splint was the only treatment for all of the included patients. The patients were assessed before the fabrication of orthosis and after 12 weeks of its use. The parameters measured were hand grip strength and the Visual Analogue Scale for pain and paraesthesia. The patients further completed the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) and a shorter version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH). Results: In the first group, a statistically significant improvement was established in paraesthesia and hand grip strength (p = 0.019, p = 0.024, respectively), but there was no statistically significant improvement in pain, and the results of both BCTQ and QuickDASH. In the second group, a statistically significant improvement was found in paraesthesia, the BCTQ Symptom Severity Scale and QuickDASH results (p = 0.008, p < 0.001, p = 0.011, respectively), whereas no statistically significant improvement was established in pain, hand grip strength and the BCTQ Functional Status Scale. However, when comparing the change in the outcome measures between the 2 groups, no statistically significant differences were found. Conclusions: This study has shown that 12-week night-time splinting is beneficial not only for patients with mild CTS but also for those with advanced CTS, and those awaiting surgical treatment. Therefore, splinting is recommended for all patients with CTS. Int J Occup Med Environ Health. 2020;33(6):771–80