OBJECTIVE To describe a safe long-term medical treatment for deeply infiltrating endometriosis, a critical condition characterized by multiple painful symptoms and a high recurrence rate after surgical treatment. METHODS Prospective study. METHODS University of Siena. METHODS Twenty-one women with deeply infiltrating endometriosis. METHODS In a nonrandomized prospective study a low dose of vaginal danazol (200 mg/d) was self-administered for 12 months. After a previous laparoscopic surgery, these patients had reported recurrent severe dyspareunia, dysmenorrhea, and pelvic pain (in five cases also painful defecation). METHODS Before and every 3 months during the treatment a visual analogue pain scale was used. Transvaginal and transrectal ultrasound examinations were performed before and after 6 and 12 months of treatment. Adverse effects were registered, and serum concentration of cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glycemia, protein S, protein C, antithrombin III, and homocysteine was evaluated before and after 12 months. RESULTS Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased within 3 months and disappeared after 6 months of treatment, with a persistent effect during the 12 months of treatment. A relief of painful defecation was also shown. Ultrasound examination showed a reduction of the nodularity in the rectovaginal septum within 6 months. The medical treatment did not affect metabolic or thrombophilic parameters; few local vaginal adverse effects were reported. CONCLUSIONS Vaginal danazol resulted in effective medical treatment for the various painful symptoms in women with recurrent deeply infiltrating endometriosis, and because of the lack of significant adverse effects it may be proposed as an alternative to repeated surgery.