BACKGROUND: Emergency departments (EDs) play an essential role in the timely initiation of HIV post-exposure prophylaxis (PEP) for sexual assault victims. METHODS: Retrospective analysis of sexual assault victims evaluated and offered HIV PEP in an urban academic ED between January 1, 2005 and January 1, 2018. Data on demographics, comorbidities, nature of sexual assault, initial ED care, subsequent healthcare utilization within 28 days of initial ED visit, and evidence of seroconversion within 6 months of the initial ED visit were obtained. Predictors of subsequent ED visit and follow-up in the infectious diseases clinic were evaluated using logistic regression analysis. RESULTS: Four hundred twenty-three ED visits met criteria for inclusion in this study. Median age at ED presentation was 25 years (IQR 21-34 years), with the majority of victims being female (95.5%), Black (63.4%), unemployed (66.3%) and uninsured (53.9%); psychiatric comorbidities (38.8%) and substance abuse (23.6%) were common. About 87% of the patients accepted HIV PEP (368 of 423 ED visits). Age (OR 0.97, 95% CI 0.94-0.99, p = 0.025) and sexual assault involving >1 assailant (OR 0.48, 95% CI 0.26-0.88, p = 0.018) were associated with lower likelihood of HIV PEP acceptance. Ten patients (2.7%) followed up with the infectious disease clinic within 28 days of starting HIV PEP; 70 patients (19%) returned to the ED for care during the same time period. Psychiatric comorbidity (OR 2.48, 95% CI 1.43-4.30, p = 0.001) and anal penetration (OR 2.02, 95% CI 1.10-3.70, p = 0.024) were associated with greater likelihood of repeat ED visit; female gender (OR 0.30, 95% CI 0.11-0.85, p = 0.023) was associated with lower likelihood of repeat visit. Completion of HIV PEP was documented for 14 (3.3%) individuals. CONCLUSIONS: While ED patient acceptance of HIV PEP after sexual assault was high, infectious disease clinic follow-up and documented completion of PEP remained low. Innovative care models bridging EDs to outpatient clinics and community support services are needed to optimize transitions of care for sexual assault victims, including those receiving HIV PEP.