Incidence of HIV infection remains high in New York City and, while considerable attention has been paid to the scale-up of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP) plays an important role in the HIV prevention continuum. We conducted a retrospective analysis of clinical and demographic characteristics of individuals receiving HIV post-exposure prophylaxis at a large academic medical center in northern Manhattan. Post-exposure prophylaxis users were predominantly Latinx (52.8%) and/or African American (33.7%) men who have sex with men (72%), representing the underserved groups at highest risk of HIV infection. Many individuals (20%) requiring PEP presented to their clinician seeking initiation of PrEP. Frequent PEP users may be good candidates for PrEP but psychosocial barriers such as home environment and recreational drug use must be addressed for successful transitions. Patient counseling for at-risk groups should involve both PEP and PrEP screening and must be sensitized to the needs and cultures of the communities they serve.