Objectives. To perform a comparative evaluation and follow-up of patients with erectile dysfunction (ED) who were treated with intracavernous injection of vasoactive drugs, starting with simple drugs and advancing to complex combinations. Methods. The study included 625 patients, 26 to 85 years old, with ED. Four intracavernous injection protocols were used: protocol 1, papaverine plus phentolamine; protocol 2, prostaglandin E1; protocol 3, papaverine, phentolamine, and prostaglandin E1; and protocol 4, atropine sulfate, papaverine, phentolamine, and prostaglandin E1. A positive response was defined as an erection sufficient for penetration. Patients for whom the basic protocol failed were successively switched to the more advanced protocols until a positive response was achieved. Results. A positive response was achieved by 415 (66.4%) of the 625 patients given protocol 1; 75 (36%) of the remaining 210 patients given protocol 2; 98 (72.6%) of the 135 patients given protocol 3; and 22 (59.5%) of 37 patients given protocol 4. All four protocols failed in only 15 patients (2.4%). At the 3-year follow-up visit (n = 610), 349 had achieved coitus, 65 (10.6%) without an injection and 202 (33.1%) with an injection. Eighty-two patients sometimes performed coitus without an injection. Sixty-three patients (10.3%) abandoned the program because of marital or health problems; 198 asked to be switched to Viagra during the follow-up period, and 120 returned to the program. Conclusions. Overall, our progressive treatment yielded a high positive response rate (97.6%), with 57.2% achieving successful coitus on follow-up. The main advantage of the program is that it spares patients who are responsive earlier from using more complex, painful, and costly drugs. Copyright (C) 2000 Elsevier Science Inc.