This investigation examined how prospective memory (PM) relates to cognitive abilities (i.e., executive function, attention, working memory, and retrospective memory) and brain structure in adolescents who vary in prenatal drug exposure (PDE). The sample consisted of 105 (55 female and 50 male) urban, primarily African American adolescents (mean age=15.5years) from low socioeconomic status (SES) families. Approximately 56% (n =59) were prenatally exposed to drugs (heroin and/or cocaine) and 44% (n =46) were not prenatally exposed, but the adolescents were similar in age, gender, race, and SES. Executive functioning, attentional control, working memory, retrospective memory, and overall cognitive ability were assessed by validated performance measures. Executive functioning was also measured by caregiver report. A subset of 52 adolescents completed MRI (magnetic resonance imaging) scans, which provided measures of subcortical gray matter volumes and thickness of prefrontal, parietal, and temporal cortices. Results revealed no differences in PM performance by PDE status, even after adjusting for age and IQ. Executive function, retrospective memory, cortical thickness in frontal and parietal regions, and volume of subcortical regions (i.e., putamen and hippocampus) were related to PM performance in the sample overall, even after adjusting for age, IQ, and total gray matter volume. Findings suggest that variations in PM ability during adolescence are robustly related to individual differences in cognitive abilities, in particular executive function and retrospective memory, and brain structure, but do not vary by PDE status.