To determine effectiveness and safety of colchicine in Peyronie's disease. In all, 84 patients with Peyronie's disease who did not have calcified plaque were entered into study. The mean disease duration was 15 months. A medical history was obtained, and physical examination, penile X-ray, and dynamic penile duplex ultrasound were performed. Patients were randomly divided into group 1, those who received 0.5–2.5 mg colchicine daily for 4 months and group 2, who received placebo for the same period. Response to therapy was assessed objectively, during dynamic penile duplex ultrasound, as well as subjectively using International Index of Erectile Function (IIEF) questionnaire and measurements of pain, duration of disease, penile curvature, and plaque size. Differences before and after treatment and among the three Kelami classification groups were assessed. In total, 78 (92.8%) completed the whole treatment schedule. Pain resolved in 60 and 63.6% of the patients treated with colchicine and placebo, respectively (P>0.05). After therapy, in subjects and controls a reduction in the penile deformity was observed by 17.1 and 18.4% of the patients (P>0.05), and a decrease in plaque size was noticed by 10.5 and 10%, respectively (P>0.05). Objective measurements did not demonstrate any difference in plaque size or penile curvature. There were no substantial differences in response to treatment based on duration of disease or within the three Kelami classification groups. Significant drug-related adverse effects occurred in colchicine group and in two cases was treatment discontinued. Colchicine is no better than placebo in improvement of pain, curvature angle, or plaque size in patients with Peyronie's disease.