INTRODUCTION: Overactive bladder syndrome (OAB) is a chronic disorder that often requires long-term treatment. There is a growing interest in new substances. In vitro experiments of Bryophyllum pinnatum (BP) on porcine bladder muscle have shown a muscle-relaxing effect. In this clinical trial we evaluated BP versus placebo regarding efficacy and safety. MATERIALS AND METHODS: Prospective, double-blind randomized, placebo-controlled study with 20 patients (10 BP, 10 placebo); medication over 8 weeks; dosage 3×2 capsules BP 50% (350mg)/day or placebo (lactose). Primary aim: reduction of the micturition frequency/24h. Secondary aim: change in quality of life, alterations of parameters in the bladder diary and adverse events (AE). Statistical analysis was performed with IBM SPSS Statistics 20. The groups were compared using Fisher's exact test and the Mann-Whitney test; the visits using the Wilcoxon signed ranks test. RESULTS: Both groups did not differ significantly in demographical data. For the primary endpoint, a trend in the reduction of the micturition frequency/24h in the BP group was found: 9.5±2.2 before and 7.8±1.2 after BP versus 9.3±1.8 before and 9.1±1.6 after placebo, p=0.064. From visit 2 to visit 4, micturition frequency/24h improved in 8/10 patients in the BP group (p=0.037). In the placebo group, micturition frequency/24h improved in 5/9 patients (p=0.89). Improvement of the QoL did not differ between the two groups. The incidence of AE was similar in both groups, no SAE occurred. CONCLUSION: The successful safety outcome and positive trend for efficacy permits BP to be further evaluated as a favorable treatment option for OAB.