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To examine opioid use, opioid prescribing patterns, and timing of the first opioid prescription in endometriosis patients compared with matched women in the control group without endometriosis.We conducted a retrospective analysis of the Clinformatics Datamart database. Women diagnosed with endometriosis from January 2006 through December 2016 and aged 18–49 years were compared with women in the control group matched on age, region, race, insurance payer, and plan type. Key outcomes included: filled prescription for an opioid, multiple opioid prescriptions, number of days' supply, daily dose (morphine milligram equivalents), and concomitant opioid and benzodiazepine prescriptions. Cohorts were descriptively analyzed using t- and χ2 statistics and multivariable regression analyses yielded adjusted relative risk (RR) ratios and 95% CI.The study sample included 53,847 endometriosis patients and 107,694 patients in the control group. The mean age was 38 years, 62.4% of patients were white, and 51.6% lived in the South. Women in the endometriosis case group, compared with women in the control group, were more likely to fill an opioid prescription (42,705 [79.3%] women in the case group vs 26,106 [24.2%] women in the control group; adjusted RR ratio 2.91; 2.87–2.94), had higher likelihood of filling prescriptions with a dose of 50 morphine milligram equivalents or more (24,544 [45.6%] vs 10,463 [9.7%]; adjusted RR ratio 4.07; 3.98–4.16) or 100 morphine milligram equivalents or more (8,013 [14.9%] vs 3,582 [3.3%]; adjusted RR ratio 3.56; 3.43–3.70). Women in the case group were more likely to have concomitant opioid and benzodiazepine prescriptions (5,453 [10.1%] vs 3,711 [3.5%]; adjusted RR ratio 1.95; 1.88–2.03) and to have used these drugs concurrently for at least 30 days (1,596 [3.0%] vs 1,265 [1.2%]; adjusted RR ratio 1.43; 1.34–1.52) or at least 90 days (875 [1.6%] vs 777 [0.7%]; adjusted RR ratio 1.27; 1.17–1.37). Similar results were obtained after excluding opioid prescriptions received during a 30-day postsurgery window.Women with endometriosis had higher probabilities of prolonged use of opioids and concomitant use with benzodiazepines compared with women without this condition.This study was funded by AbbVie, Inc.