Objective To detect whether oral acetyl-L-carnitine might be useful in the acute and early chronic phases of Peyronie's disease, compared with tamoxifen, a drug currently in use. Patients and methods The study included 48 patients with Peyronie's disease (15 acute and 33 initial chronic), randomized equally into two groups, The fist group used tamoxifen 20mg twice daily for 3 months and the second acetyl-L-carnitine Ig twice daily for 3 months, The disease and stages were diagnosed and identified using a history, objective examination, pharmacologically induced erection, autophotography during erection, and basic and dynamic colour Doppler ultrasonography, Penile curvature, plaque size, pain and disease progression were assessed. The differences between the groups or between the variables before and after therapy were compared using analysis of variance or the chi-squared test. Results Acetyl-L-carnitine was significantly more effective than tamoxifen in reducing pain and in inhibiting disease progression. Acetyl-L-carnitine reduced penile curvature significantly, while tamoxifen did not; both drugs significantly reduced plaque size. Tamoxifen induced significantly more side-effects than acetyl-L-carnitine. Conclusions These results suggest that acetyl-L-carnitine is significantly more effective and safe than tamoxifen in the therapy of acute and early chronic Peyronie's disease.