Background: Brain-derived neurotrophic factor (BDNF) shows consistent associations with memory across many clinical populations, including dementia. Less is understood about the association between BDNF and memory functioning in people living with HIV (PWH). Methods: A sample of 173 adults aged 50+ (n = 100 HIV+ and n = 73 HIV seronegative) completed a comprehensive neurobehavioral assessment and blood draw. Linear regressions predicting memory domains (learning, delayed recall, and recognition) were conducted including race (White vs. Black/African American), HIV status, BDNF, and their interactions. Results: For learning and delayed recall, significant (P, 0.05) main effects for race and interactions for BDNF x race and HIV status x race were found, whereas for recognition, only a BDNF x race interaction emerged. In adjusted models, BDNF x race interactions remained for learning and delayed recall. To determine effect size, correlations were conducted between BDNF and memory domains stratified by HIV serostatus and race, and small-medium associations between BDNF and learning and delayed recall (rho = 0.29, P, 0.01; rho = 0.22, P = 0.045), but no recognition (rho = 0.12, P = 0.29) were found among Black/African American PWH. BDNF was not significantly associated with memory domains in White PWH or either HIV- sample. Follow-up analyses showed BDNF-memory specificity, such that race X BDNF interactions did not emerge for other cognitive domains. Conclusions: While limited by cross-sectional design among a small sample, particularly of White individuals, results indicate that BDNF may serve as a promising biomarker reflecting memory functioning in PWH, particularly Black/African Americans. Further work is needed to replicate findings and determine mechanisms for racial differences in BDNF associations with memory.