Objectives To determine, in a prospective randomized, double‐blind placebo‐controlled study, the effect of 6 weeks of high‐dose (5 g/day) orally administered nitric oxide (NO) donor l‐arginine on men with organic erectile dysfunction (ED). Patients and methods The study included 50 men with confirmed organic ED who were randomized after a 2‐week placebo run‐in period to receive l‐arginine or placebo. A detailed medical and sexual history, O’Leary's questionnaire, a specially designed sexual function questionnaire and a sexual activity diary were obtained for each patient. All participants underwent a complete physical examination including an assessment of bulbocavernosus reflex and penile haemodynamics. Plasma and urine nitrite and nitrate (designated NOx ), both stable metabolites of nitric oxide, were determined at the end of the placebo run‐in period, and after 3 and 6 weeks. Results Nine of 29 (31%) patients taking l‐arginine and two of 17 controls reported a significant subjective improvement in sexual function. All objective variables assessed remained unchanged. All nine patients treated with l‐arginine and who had subjectively improved sexual performance had had an initially low urinary NOx , and this level had doubled at the end of the study. Conclusions Oral administration of l‐arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production. The haemodynamics of the corpus cavernosum were not affected by oral l‐arginine at the dosage used.