Objective: To review the available clinical evidence on the use of combined hormonal contraceptive (CHC) agents (estrogen [E]-progestin combinations) for the treatment of endometriosis-related pain. Design: A systematic review of the MEDLINE, Embase, and Derwent Drug File databases for prospective clinical studies. Setting: Not applicable. Patient(s): Women with endometriosis diagnosed by validated means. Intervention(s): Combined hormonal contraceptive agents, active comparators, placebo, or no treatment. Main Outcome Measure(s): Endometriosis-related pain (dysmenorrhea, pelvic pain, and dyspareunia). Result(s): Nine randomized controlled trials and nine observational studiesmet the inclusion criteria. The quality of datawas low: only two of the nine randomized trialswere placebo controlled, andmost trialswere not blinded. The CHC agents were reported to significantly reduce dysmenorrhea, pelvic pain, and dyspareunia frombaseline in most studies; continuous administration seemed to be more useful than cyclic administration. The effectiveness of CHC agents for pain reduction was similar to or less than that of oral progestins and GnRH agonists. Conclusion(s): The available literature suggests that CHC treatment is effective for relief of endometriosis-related dysmenorrhea, pelvic pain, and dyspareunia; however, the supportive data are of low quality. Furthermore, insufficient data exist to reach conclusions about the overall superiority of any given CHC therapy, and the relative benefit in comparison to other approaches. Additional high-quality studies are needed to clarify the role of CHC agents and other treatments in women with endometriosis-related pain. (c) 2018 The Authors. Published by Elsevier Inc. on behalf of the American Society for Reproductive Medicine.