ABSTRACT Youth at-risk for HIV are also at-risk for mental health disorders and psychiatric hospitalization. Understanding the association between engagement in HIV prevention, concurrent risk behaviors, and psychiatric hospitalization may lead to improvements in integrated prevention and mental health treatment efforts. Youth at-risk for HIV, aged 14–24 years old, predominantly Black/African American and Latinx (75%) were recruited through youth-serving clinics and community sites in Los Angeles (n = 839) and New Orleans (n = 647). We compared youth with and without histories of psychiatric hospitalization on engagement in HIV prevention, concurrent risk behaviors, and demographic characteristics. We examined predictors of hospitalization using multiple imputations for missing data. Hospitalized youth (30%) were more involved in HIV programs, but were less likely to use PrEP/PEP or condoms than non-hospitalized youth. The odds of hospitalization were higher for transgender/gender nonconforming youth relative to cisgender youth; the OR was increased after adjustment for concurrent risk behaviors. Hospitalization was associated with homelessness, trauma, incarceration, substance use, and involvement in substance abuse treatment programs. There is a continuing need to integrate the diagnosis and treatment of mental health disorders into HIV prevention programs to better address multiple challenges faced by vulnerable youth.