Introduction & Objectives: A reduced nocturnal bladder capacity (RNBC) is one of the causes of resistant mono-symptomatic nocturnal enuresis (MNE) to desmopressin treatment. RNBC is defined when nocturnal urine production is less than the maximum voided volume in the daytime. Anticholinergic drugs are used to increase bladder capacity and to decrease overactivity. Mirabegron (selective B3 agonist) efficacy and safety in treating children with neurogenic bladder have been proved in many studies. We aim to assess the efficacy and safety of adding Mirabegron and Solifenacin to the enuresis alarm (EA) in the management of MNE in children with RNBC. Materials & Methods: We included all consecutive MNE patients with RNBC after approval of our local committee on ethics in human investigation to receive Mirabegron 50 mg, Solifenacin 5 mg or placebo in addition to EA. Patient demographics, MVV, NUP and the percentage of wet nights in a week before enrollment were collected. Primary endpoints were the reduction in the percent of wet nights and the improvement in NBC. Secondary endpoints were the adverse events and adverse effect related drug discontinuation rates. Results: 141 patients were randomly allocated in 3 groups. There were no significant differences between the 3 groups regarding patients' ages, MVV, NUP, or the percent of wet nights (p value 0.335, 0.209, 0.879, and 0.160 respectively). After 3 months of treatment, Mirabegron showed more efficacy than Solifenacin in reduction of wet nights percentages and improving the NBC with no significant difference between them regarding the number of wet nights with NUP< MVV. After 6 months, mirabegron and solifenacin were significantly more effective than placebo in reduction of wet nights percentages, improve NBC and decreasing number of nights with NUP<MVV with no significant difference between them (Table 1). Mirabegron has a significantly lower adverse effect discontinuation rates than Solifenacin 2/47, and 9/47 respectively (p value 0.025). Conclusions: Mirabegron is more effective than Solifenacin in treating MNE with RNBC with a better safety profile and lower discontinuation rate due to drug adverse effect.