OBJECTIVE: To determine the efficacy of GnRH analogue plus add-back therapy compared with GnRH analogue alone and estroprogestin in patients with relapse of endometriosis-associated pain. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENT(S): One hundred thirty-three women with relapse of endometriosis-related pain after previous endometriosis surgery. INTERVENTION(S): Forty-six women were treated with GnRH analogue plus add-back therapy, 44 women were given GnRH analogue alone, and 43 women received estroprogestin, for 12 months. MAIN OUTCOME MEASURE(S): Pain evaluation by a visual analogue scale, quality of life in treated patients according to the SF-36 questionnaire, and occurrence of adverse effects, including bone mass density loss, at pretreatment, after 6 months of treatment, at the end of treatment (12 months), and 6 months after discontinuation of treatment. RESULT(S): Patients treated either with GnRH analogue alone or GnRH analogue plus add-back therapy showed a higher reduction of pelvic pain, dysmenorrhea, and dyspareunia than patients treated with oral contraceptive, whereas patients treated with add-back therapy showed a better quality of life, as assessed with the SF-36 questionnaire, and adverse effects rate than the other two groups. CONCLUSION(S): Add-back therapy allows the treatment of women with relapse of endometriosis-associated pain for a longer period, with reduced bone mineral density loss, good control of pain symptoms, and better patient quality of life compared with GnRH analogue alone or oral contraceptive.