The present study assesses the effectiveness of our progressive treatment program for erectile dysfunction in patients with cardiovascular diseases. The study sample included 453 patients aged 36 to 91 years. Therapy in all patients was begun with sildenafil citrate 25 to 100 mg. Those with contraindications, drug adverse effects, or a negative response (erection insufficient for vaginal penetration) were given intracavernous injections of a cocktail of vasoactive drugs (dimix, trimix, or quadmix), followed by the addition of sildenafil citrate to the trimix in case of failure, and then a penile prosthesis. Patients were followed for 2 years; in cases of treatment ineffectiveness during follow-up, drug dosages were increased or a penile prosthesis was suggested. Sildenafil citrate was offered to 417 patients of whom 205 (49.2%) responded positively. The remaining 248 patients received intracavernous injections: 135 (54.4%) had a positive response to the dimix, 85 (75.2%) to the trimix, and 16 (57.1%) to the quadmix. Four of the other 12 patients (0.9%) responded to sildanefil citrate + trimix, and 2 (0.4%) agreed to a penile prosthesis. At the 2-year follow-up of 447 patients, 131 (29.3%) were successfully treated with sildanefil citrate, 92 (20.6%) with dimix, 122 (27.3%) with trimix, 12 (2.7%) with quadmix, and 2 (0.4%) with sildanefil citrate + trimix; 5 patients (1.1%) had a penile implant. Forty-eight patients (10.7%) achieved spontaneous erection, of whom 46 were taking aspirin. Twenty-six patients (5.8%) stopped treatment because of health and family reasons and 9 (2%) had a negative response. Our progressive treatment program for erectile dysfunction has a high success rate in patients with cardiovascular disease: Overall, 98.7% achieved an erection sufficient for vaginal penetration immediately after the trial and 92.2% on follow-up; 10.7% achieved spontaneous erections.