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The Institute of Medicine and The Joint Commission recommend routine documentation of patients’ sexual orientation in health care settings. Currently, very few health care systems collect these data since patient preferences and health care professionals’ support regarding collection of data about patient sexual orientation are unknown.To identify the optimal patient-centered approach to collect sexual orientation data in the emergency department (ED) in the Emergency Department Query for Patient-Centered Approaches to Sexual Orientation and Gender Identity study.An exploratory, sequential, mixed-methods design was used first to evaluate qualitative interviews conducted in the Baltimore, Maryland, and Washington, DC, areas. Fifty-three patients and 26 health care professionals participated in the qualitative interviews. Interviews were followed by a national online survey, in which 1516 (potential) patients (244 lesbian, 289 gay, 179 bisexual, and 804 straight) and 429 ED health care professionals (209 physicians and 220 nurses) participated. Survey participants were recruited using random digit dialing and address-based sampling techniques.Qualitative interviews were used to obtain the perspectives of patients and health care professionals on sexual orientation data collection, and a quantitative survey was used to gauge patients' and health care professionals' willingness to provide or obtain sexual orientation information.Mean (SD) age of patient and clinician participants was 49 (16.4) and 51 (9.4) years, respectively. Qualitative interviews suggested that patients were less likely to refuse to provide sexual orientation than providers expected. Nationally, 154 patients (10.3%) reported that they would refuse to provide sexual orientation; however, 333 (77.8%) of all clinicians thought patients would refuse to provide sexual orientation. After adjustment for demographic characteristics, only bisexual patients had increased odds of refusing to provide sexual orientation compared with heterosexual patients (odds ratio, 2.40; 95% CI, 1.26-4.56).Patients and health care professionals have discordant views on routine collection of data on sexual orientation. A minority of patients would refuse to provide sexual orientation. Implementation of a standardized, patient-centered approach for routine collection of sexual orientation data is required on a national scale to help to identify and address health disparities among lesbian, gay, and bisexual populations.