OBJECTIVE: To determine whether domain-specific neurocognitive (NC) impairments predict falls in HIV+ compared with HIV- women. DESIGN: Cross-sectional data analysis from 825 HIV+ and 392 HIV- women in the Women's Interagency HIV Study with NC testing within 2 years before falls surveys. METHODS: NC impairment (T score <40) was assessed in 7 domains: executive function, psychomotor speed, attention, learning, memory, fluency, and fine motor function. For domains associated with any fall within 6 months in simple logistic regression (P < 0.05), hierarchical regression models evaluated associations between NC impairment and odds of falling, adjusting for: (1) study site and HIV, (2) demographics, (3) comorbid conditions, (4) substance use/central nervous system active medications, and HIV-specific factors. RESULTS: Median age was higher in HIV+ than HIV- women (51 vs. 48 yrs); prevalence of falls was similar (19% HIV+, 16% HIV-). Overall, executive function [OR (odds ratio) = 1.82, 95% CI (confidence interval): 1.21 to 2.74; P = 0.004], psychomotor speed (OR = 1.59, 95% CI: 1.05 to 2.42, P = 0.03), and fine motor (OR 1.70, 95% CI: 1.11 to 2.61, P = 0.02) impairments were associated with greater odds of falls in fully adjusted models. In fully adjusted models, associations of executive function, psychomotor speed, and fine motor were nonsignificant among HIV+ women; conversely, among HIV- women, associations with impaired executive and fine motor functions were strengthened and remained significant. CONCLUSIONS: Cognitive impairment was associated with falls among middle-aged HIV- but not HIV+ women. Additional studies should elucidate mechanisms by which domain-specific NC impairment impacts fall risk among older HIV+ and HIV- women and how different factors modify relationships between cognition and falls.