The present pilot study compared the ability of a conventional patient complaint-driven approach to that of nucleic-acid amplification testing (NAAT) of urine to identify those individuals among an adult, urban, Emergency Department (ED) population infected with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Urine for NAAT was collected for testing after individuals had completed a questionnaire and before being seen by a physician. A total of 614 subjects were enrolled, and complete physical examinations were performed on 348 (56.6%) individuals, with women being significantly more likely to receive such an evaluation (odds ratio [OR] 3.09; 95% confidence interval [CI] 1.96-4.86); p < 0.001). A total of 153 (24.9%) of the study cohort tested positive for a least one sexually transmitted disease (STD), and only a reported history of STD (OR 1.74; 95% CI (1.18-2.57); p = 0.005) and a history of a new sexual partner in the last 3 months (OR 1.79; 95% CI 1.13-2.82); p = 0.012) were predictive of a positive STD test. NAAT of urine samples on patients who did not receive a complete physical examination resulted in a 33% (51/153) increase in diagnostic yield in this cohort of ED attendees.