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National guidelines recommend annual Chlamydia trachomatis and Neisseria gonorrhoeae screening for sexually active youth at risk for infection. These infections have serious sequelae in women if untreated, and methods to improve testing are needed. We hypothesize that an electronic method of identifying at-risk youth will significantly increase testing for these sexually transmitted infections during emergency department (ED) visits.We developed an audio-enhanced computer-assisted self-interview (ACASI) to obtain sexual histories from ED patients and an embedded decision tree to create a sexually transmitted infection testing recommendation. ED health care providers were prompted by the electronic medical record to review the participant answers and testing recommendations, and to offer testing to at-risk youth. Patients aged 15 to 21 years and visiting the St. Louis Children's Hospital ED, regardless of complaint, were eligible for participation.Sexually transmitted infection testing among all 15- to 21-year-old ED patients increased from 9.3% in the 3 months before the ACASI to 17.8% during the 8-month period the ACASI was available and diminished to 12.4% in the 3 months after ACASI withdrawal (P<.001). During the ACASI period, we approached 51.4% of eligible patients and enrolled 59.8% (800/1,337) of those approached. Among ACASI participants, 52.4% (419/800) received a recommendation to receive sexually transmitted infection testing. Of these patients, 52.7% (221/419) received testing in the ED and 18.1% (40/221) of those tested had positive results for chlamydia or gonorrhea, 55% of whom (22/40) had chief complaints unrelated to sexually transmitted infections. Most participants (89%) rated the ACASI easy to use.Sexually transmitted infection testing in the ED significantly increased during ACASI use and diminished after withdrawal. The ACASI was well accepted by youth and holds promise for enhancing sexually transmitted infection testing in the ED.