Both HIV and aging impact performance on neuropsychological testing; however, evidence for differences between HIV effects in younger compared to older subjects (interaction effects) is limited and the findings have been inconsistent. Coexisting morbidities that contribute to cognitive impairment in HIV include those not directly referable to infection, per se, and are more prevalent with advancing age, increasing the likelihood that HIV and age effects may be largely independent. As individuals survive with HIV into geriatric age groups, greater clarity on these relationships is essential. We present cross-sectional data from a large (n = 450) cohort designed to analyze HIV, age, and interaction effects using a well-matched cohort of HIV-negative individuals. Results reveal limited evidence for interaction effects between HIV and age on neuropsychological performance. We conclude that older age does not significantly influence neuropsychological performance among HIV patients when seronegative controls are largely composed of individuals from a similar socioeconomic background.