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PURPOSE The purpose of the study was to estimate the effect of exposure to neighborhood poverty in adolescence on HIV/STI prevalence in early adulthood. METHODS Longitudinal data from three waves of the National Longitudinal Study of Adolescent to Adult Health were analyzed. The primary exposure was living in a high- versus medium/low-poverty neighborhood during wave I. The outcome was having a sexually transmitted infection (STI) or receiving a HIV/STI diagnosis in the past 12 months at wave III. Covariates included sociodemographic, behavioral, and mental health-related factors. Inverse probability weighted marginal structural models were used to estimate neighborhood poverty-based differences in HIV/STI prevalence. RESULTS The analytic sample comprised 8232 National Longitudinal Study of Adolescent to Adult Health participants. Of these, 16% and 84% resided in high- and medium/low-poverty neighborhoods, respectively. Eleven percent currently had an STI or HIV/STI diagnosis within the prior 12 months. Accounting for measured potential sources of confounding and selection bias, the HIV/STI prevalence difference (95% confidence limits) for those who grew up in high- versus medium/low-poverty neighborhoods was 0.015 (-0.015, 0.045). CONCLUSIONS Strong evidence for neighborhood poverty-based differences in HIV/STI prevalence was not observed. Researchers should continue to investigate the effect of neighborhood-level socioeconomic position measures and, if warranted, identify etiologically relevant exposure periods.