Introduction & Objective: Nocturnal enuresis as a common disorder in children can create many problems. A variety of modalities has been used for its treatment but applying new and effective modalities can be of much interest. In this study efficacy of interferential currents (IFC), as a new modality, has been compared with nasal spray of desmopressin in treatment of primary nocturnal enuresis in 5-15 year old children. Materials & Methods: This is a prospective, randomized, clinical trial in which 39 patients received desmopressin (20µg/day) for 3 weeks and left off gradually in six months, if it was responsive. The other 36 patients received IFC therapy (5 times/week, 20 minutes each session, up to 15 sessions). Efficacy of treatment was evaluated after completion of therapeutic sessions and recurrence rate was calculated one month later. Results: About 66.7% of patients were 5-10 and 33.3% were 11-15 years old. Of all subjects, 58.7% were male and 41.3% were female. In those patients who received IFC, complete response was observed in 25%, partial response in 36.1% and 38.9% had no response while in desmopressin group, complete response was achieved in 61.5%, and partial response in 25.6% of cases and 12.8% had no response to the treatment. The recurrence rate in IFC and desmopressin groups were 16.7 % and 23.1%, respectively. In 11-15 year old children, response rate was better than those for 5-10 years old. Male patients had the most rate of recurrence. Therapeutic side effects were not observed in any of the patients in both groups. Conclusion: Desmopressin and IFC are effective and safe modalities for treatment of primary nocturnal enuresis of children with less recurrence in females. Moreover, desmopressin had better efficacy while IFC had less recurrence rate. In addition, desmopressin showed better efficacy in females. IFC can be recommended as an effective and safe modality for treatment of primary nocturnal enuresis, with less recurrence rate.