To define the role of phonophoresis and iontophoresis of corticosteroids in conjunction with wrist splint use in the treatment of carpal tunnel syndrome (CTS) compared to wrist splint use alone, 52 CTS subjects were analyzed based on clinical and electrophysiological criteria. A prospective, randomized controlled trial was carried out to assess symptom severity, motor skills, and hand function according to the Boston Symptom Severity Scale (BSSS), grip strength, and nine-hole peg test (NHPT), respectively, on the initial visit and in the 3rd month after treatment. The patients underwent conservative interventions randomly as follows: (1) 3 weeks of phonophoresis with betamethasone in conjunction with wrist splint use (group I, n: 18) or (2) 3 weeks of iontophoresis with betamethasone in conjunction with wrist splint use (group II, n: 16) or (3) wrist splint use alone (control, group III, n: 18). The mean age of the patients was 43.7 ± 8.4 (range 24-57) years. Groups I, II, and III showed a significant and further improvement in BSSS at the 3rd month evaluations compared with baseline (P < 0.001, P = 0.001, P < 0.001, respectively), but no significant change was observed in grip strength or NHPT (P > 0.05). There was a statistically significant difference between the phonophoresis and control groups after treatment only regarding BSSS, in favor of phonophoresis (P = 0.012). We recommend the use of wrist splints especially with phonophoresis for relief of symptoms in patients with CTS. Our results demonstrated no superiority among the treatment groups. Further, transdermal steroid treatments are not key determinants of efficacy with respect to motor skills and hand dexterity.