Youth with perinatal HIV infection (PHIV) are at increased risk for neurocognitive impairment (NCI). Prospective memory (PM) is a complex neurocognitive function that has been shown to be impaired in adults with HIV disease and independently associated with poorer daily living skills, including medication nonadherence. The current study sought to determine the presence and extent of PM deficits in youth with PHIV. Participants included 173 youth with PHIV and 85 youth perinatally HIV-exposed but uninfected (PHEU), mean age 14.1 years, 75% black, 18% Hispanic. Among youth with PHIV, 26% had a past AIDS-defining condition (Centers for Disease Control and Prevention [CDC], Class C), 74% did not (non-C). Adjusted generalized estimating equation models were used to compare groups (PHIV/C, PHIV/non-C, and PHEU) on the Naturalistic Event-Based Prospective Memory Test (NEPT) and the Prospective Memory Assessment for Children & Youth (PROMACY). Secondarily, subgroups defined by HIV serostatus and global NCI were compared (PHIV/NCI, PHIV/non-NCI, PHEU). PHIV/C had significantly lower NEPT scores than PHEU, with decreases of 40% in mean scores, but did not differ from PHIV/non-C. PHIV/NCI had 11-32% lower PROMACY scores and 33% lower NEPT scores compared to PHIV/non-NCI (all p < .05); significantly, lower scores for PHIV/NCI versus PHEU also were observed for PROMACY and NEPT indices. Findings suggest a subset of youth with PHIV (those with a prior AIDS-defining diagnosis) is vulnerable to PM deficits. The extent to which PM deficits interfere with development and maintenance of independent living and health-related behaviors during transition to adulthood requires further study.