No oral medication has proved to be clearly beneficial for Peyronie's disease (PD). We investigated the safety and efficacy of coenzyme Q(10) (CoQ(10)) supplementation in patients with early chronic PD. We conducted a randomized clinical trial of 186 patients with chronic early PD. Patients were randomly assigned to either 300 mg CoQ(10) daily (n=93) or similar regimen of placebo (n=93) for 24 weeks. Erectile function (EF), pain during erection, plaque volume, penile curvature and treatment satisfaction using patient versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire were assessed at baseline and every 4 weeks during study period. EF was assessed using International Index of Erectile Function (IIEF-5), and pain was evaluated with a visual analog scale (VAS, 0-10). All patients also responded to a Global Assessment Question, 'Has the treatment you have been taking during this study improved your erections?' After 24 weeks, mean IIEF-5 score, mean VAS score and mean EDITS score improved significantly in patients receiving CoQ(10) (all P<0.01). Mean plaque size and mean penile curvature degree were decreased in the CoQ(10) group, whereas a slight increase was noted in the placebo group (both P=0.001). Mean index of IIEF-5 in 24-week treatment period was 17.8 ± 2.7 in the CoQ(10) group and 8.8 ± 1.5 in the placebo group (P=0.001). Of the patients in CoQ(10) group, 11 (13.6%) had disease progression vs 46 (56.1%) in placebo group (P=0.01). In patients with early chronic PD, CoQ(10) therapy leads plaque size and penile curvature reduction and improves EF.