Suicide is a leading cause of death among adolescents and young adults (AYA). AYA living with perinatally-acquired HIV infection (AYALPHIV) are at higher risk of attempted suicide as compared to AYA who were perinatally HIV-exposed but uninfected (AYAPHEU). To inform interventions we identified risk and protective factors for attempted suicide among AYALPHIV and AYAPHEU. Data come from a longitudinal New York City-based study of AYALPHIV and AYAPHEU (n=339; enrollment age 9-16 years) interviewed approximately every 12-18 months. Our main outcome was suicide attempt at any follow-up. The DISC was used to assess psychiatric disorder diagnoses and attempted suicide and the Child Depression Inventory (CDI) to assess depression symptoms. Psychosocial and sociodemographic risk factors were also measured. Analyses employed backward stepwise logistic regression modeling. At enrollment, 51% were female, 49% Black, 40% Latinx, and 11% both Black and Latinx. Attempted suicide prevalence was significantly higher among AYALPHIV compared to AYAPHEU (27% vs 16%, p = 0.019) with AYALPHIV having 2.21 times the odds of making an attempt (95% CI: [1.18, 4.12], p = 0.013). Higher CDI scores were associated with an increased risk of attempted suicide in both groups and the total sample. The presence of DISC-defined behavior disorder increased risk of attempted suicide in the total sample and the AYALPHIV sub-group. Religiosity was protective of attempted suicide in AYALPHIV. AYALPHIV had increased suicide attempts compared to AYAPHEU. Religiosity was protective in AYALPHIV. Highlighting a need for prevention early mental health challenges were associated with risk. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.