Objective: To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. Patients and Methods: In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n530) or placebo therapy (n530) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. Results: The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was 23.1 points (95% CI 26.8 to 0.6, p50.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks 21.6, 95% CI 22.8 to 20.4, p50.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score 28.3, 95% CI 214.5 to 2.6) than in patients with a longer symptom duration (20.8, 95% CI 24.6 to 3