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A previous study in an inner city emergency department (ED) in Baltimore, Maryland, showed a high prevalence of gonorrhea and chlamydia infection among ED patients.The goal was to compare results from an inner city ED to results from an urban ED in Baltimore, in terms of study population and setting, risks for infection, and factors associated with nonparticipation in the study.This was a cross-sectional study of patients aged 14 to 44 years at two EDs. Outcomes for multivariate logistic regression analyses were (1) positive for gonorrhea or chlamydia by urine ligase chain reaction assay and (2) nonparticipation in the study. Comparative analyses were limited to patients aged 18 to 31 years.Patients differed significantly between EDs by participation rate, distribution of race/ethnicity, healthcare access, and behavioral risks, although the prevalence of infection did not differ. Risks for infection at the inner city ED were younger age, history of STD, and recent number of sex partners. Risks for infection at the urban ED were female gender and recent number of sex partners. At both EDs, being African American was associated with increased chance of participating, whereas lack of any genitourinary complaint was associated with nonparticipation. At the urban ED, women and patients approached for study enrollment during the day were also less likely to participate.ED-based screening for STDs can be an effective intervention for unrecognized infections. However, assessing population characteristics is necessary to develop targeted screening methods and clinical algorithms and to improve participation of patients and program sustainability.