BACKGROUND: Perinatal HIV (PHIV) infection may place youth at risk for impairments in executive functioning (EF). We examined associations of EF with HIV infection, disease severity and other factors among youth with PHIV and perinatally HIV-exposed, uninfected youth (PHEU). METHODS: Within the US-based Pediatric HIV/AIDS Cohort Study, 354 PHIV and 200 PHEU youth completed a standardized EF measure (Children's Color Trails Test, CCTT) and youth and/or caregivers completed a questionnaire measuring everyday EF (Behavior Rating Inventory of Executive Function, BRIEF). Covariates included HIV status, current and historical disease severity, demographic and caregiver variables and other cognitive measures. Analyses used linear and logistic regression and proportional odds models. RESULTS: No significant HIV status group differences were found on CCTT scores. Caregiver BRIEF ratings indicated significantly fewer problems for PHIV than PHEU youth. However, PHIV youth with past encephalopathy self-endorsed significantly greater metacognitive (ie, cognitive regulation) problems on the BRIEF and performed more slowly on the CCTT than PHEU youth. CCTT and caregiver BRIEF scores had significant associations with indicators of past and present disease severity. Both PHIV and PHEU had significantly worse scores than population means on CCTT and BRIEF; scores had significant associations with demographic covariates. CONCLUSIONS: Youth with PHIV show EF problems likely associated with risk factors other than HIV. However, cognitive slowing and self-reported metacognitive problems were evident in PHIV youth with a history of encephalopathy. Assessment and treatment of EF impairment may be important to identifying PHIV youth at particular risk for poor health and behavioral outcomes.