Abstract Objectives: To determine the effectiveness of a 6-month course of nafarelin in the treatment of stage III–IV endometriosis and to determine if pre-operative use of nafarelin facilitates surgery. Design: Prospective, multicenter, clinical trial. Setting: Eight university hospitals and two private practice institutions in France. Patients: Fifty-five patients with stage III and IV endometriosis. Two were excluded. Interventions: The severity of endometriosis was assessed at the time of laparoscopy and patients were randomized to have either laparosopic surgery at that time following 6 months of nafarelin therapy (n=28), or laparoscopic surgery following 6 months of nafarelin therapy (n=25). All had 200 μg intranasal nafarelin twice a day for 6 months and a second look laparoscopy. Main outcome measure: Clinical efficacy, tolerance to the treatment. Results: Efficacy and tolerance to the treatment were the same in both groups. AFS scores compared on both laparoscopies were significantly better if nafarelin was given prior to surgery (P=0.007). Conclusions: This preliminary study shows that in cases of combined medico-surgical treatment for stage III–IV endometriosis, preoperative medical treatment with GnRH-a gives a better AFS score improvement, but no conclusion was possible whether preoperative treatment facilitates surgery.