OBJECTIVE: Surgical correction of the deformity and plaque caused by Peyronie's disease has some important disadvantages and extracorporeal shockwave therapy (ESWT) emerged as a new promising therapy. We evaluated prospectively the efficacy and safety of the association of high dose vitamin E and ESWT as a non-invasive treatment for the disease. MATERIALS AND METHODS: Twenty-five patients 42 to 68 years old (mean = 54) presenting penile deviation and sexual distress caused by Peyronie's disease were treated in a non-invasive manner. The time of penile deviation ranged from 16 to 52 months (mean = 30). All patients had previous unsuccessful treatment for Peyronie's disease. The angulation's deformity of the penis was assessed by photography at home. The patients received vitamin E (l.200 mg daily) during 3 months and underwent 3 to 6 sessions (mean = 3) of ESWT (3,000 to 4,000 shockwaves) at a power level of l to 2 at 1-week intervals. RESULTS: From 25 patients treated, 16 (64%) reported an improvement in penile angulation, with a mean reduction of 21 degrees (10 to 40). Eight patients reported improvement in their spontaneous erections. Overall, the patients presented only minimal bruising at the site of treatment and skin hematoma. Four patients presented urethral bleeding. The mean angulation after treatment in the control group was 48.67 degrees (30 - 70) and in the study group was 24.42 degrees (0 - 70), statistically significant. CONCLUSION: Considering the common complications and the unsatisfactory outcome of the surgical correction for Peyronie's disease, the association of high dose vitamin E and ESWT represents a good option for a non-invasive, effective and safe treatment of the penile deformity.