Enuresis is identified as voluntary or involuntary leakage of urine for at least three consecutive months in the daytime and/or nighttime on clothes for children older than five. Monosymptomatic nocturnal enuresis (MNE) describes nighttime wetting without daytime leakage of urine in children with no pathology in the urinary system and it is 80% more common than enuresis. Desmopressin is the most common medical treatment for MNE. The aim of this study is to retrospectively compare the effectiveness of desmopressin as monotherapy and desmopressin + oxybutynin as a combination therapy in the treatment of nocturnal enuresis.This study retrospectively evaluated 183 patients who applied to pediatrics, pediatrics surgery and urology clinics with the complaint of nocturnal enuresis and diagnosed with primary monosymptomatic nocturnal enuresis between January 2014 and December 2019. The patients were divided into two groups (91 patients) who only received desmopressin therapy (Group 1), and those (92 patients) who received desmopressin and oxybutynin combination therapy (Group 2). Response to treatment, compliance and recurrence ratios were determined in the evaluation. Complete response was accepted as 90-100% decrease in the number of nighttime wetting, partial response was accepted as 50-90% decrease in the number of nighttime wetting and those below 50% were regarded as non-response. The 1st, 3rd, and 6th months of control data of treatment effectiveness of both groups were evaluated and their responses to treatment and the side effects of drugs were examined.The mean age 183 patients of whom 103 were male and 80 were female was 10 (6-16) year. In the first month of control of Group 1, 71.4% had a complete cure, 8.8% had a partial cure and 19.8% had no response to treatment. In the third month of control of Group 1, 74.73% gave a complete response and were cured, 5.5% gave a partial response and 19.78% had no response. In the sixth month of Group 1, 70 patients were evaluated as complete response (79.5%), and 5 patients were evaluated as partial response (5.6%). In the first month of control of Group 2, 75% gave a complete response, 10.9% gave a partial response, 14.1% had no response to treatment. In the third month of control of Group 2, 86.9% gave a complete response, 6.52% gave a partial response, and 6.52% had no response. In the sixth month of the control of Group 2, the number of patients who did not come for control and could not be reached was 2, 83 patients out of 90 patients were evaluated as complete response (92.2%), 6 patients were evaluated as partial response (6.6%).Desmopressin is the only FDA approved pharmacologic treatment for nocturnal enuresis. Desmopressin reduces urine production and the anticholinergic agent allows the bladder to store more urine. Therefore, combined therapy can be recommended in the MNE treatment for specially selected cases.