Introduction: Women prescribed Orilissa® (elagolix) for endometriosis-related pain are advised to use non-hormonal contraceptives (HC), due to a lack of clinical trial data for elagolix in combination with HCs. This study assessed (1) the impact of elagolix on effectiveness of HCs in preventing pregnancy and (2) the impact of HCs on effectiveness of elagolix in reducing pain in the real-world setting, where co-prescribing may occur. Methods: This cohort study included women aged 18-53 years who initiated elagolix or HCs from 2018 through 2021 in an administrative claims database (Optum Research Database). Women were classified into 3 cohorts, elagolix only, HC only, and elagolix + HC, and were followed from cohort entry date until occurrence of pregnancy, endometriosis-related pain, or end of follow-up. Outcomes were defined by pharmacy and medical claim codes. Cohorts were matched via propensity score to adjust for confounders. This study was determined exempt by an IRB. Results: Overall, 1,061 elagolix + HC users, 354,282 HC only users, and 1,274 elagolix only users were identified. The hazard ratio (95% confidence interval [CI]) for pregnancy in elagolix + HC users was 0.25 (0.08, 0.79) compared to HC only users. The relative risk (95% CI) for endometriosis-related pain comparing elagolix + HC users to elagolix only users was 1.01 (0.84, 1.20). Conclusion/Implications: Among women who used HCs, elagolix did not decrease the effectiveness of contraception, as defined by clinically recognized pregnancy identified using a database and, among women who used elagolix, the clinical presentation of pain was not different between HC users and non-users.