Objective: The Veterans Aging Cohort Study (VACS) Index is predictive of mortality and combines age, traditional HIV biomarkers (HIV-1 plasma RNA and current CD4 count), and non-HIV biomarkers (indicators of renal and liver function, anemia, and hepatitis C coinfection). We examined the association between the VACS Index and HIV-associated neurocognitive impairment (NCI). Design and Methods: Participants included 601 HIV-infected adults enrolled in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (ages: 18-76 years; 88% male; 63% white; median current CD4 = 364 cells/mm3; 63% on antiretroviral therapy; AIDS = 64%). Biomarkers used in calculating the VACS Index were measured in prospectively collected blood samples using conventional laboratory methods. NCI was defined using global and seven domain deficit scores. Results: Higher VACS Index scores were associated with concurrent risk for global NCI [P < 0.001; odds ratio = 1.21, confidence interval (CI): 1.12 to 1.32], even when adjusting for psychiatric comorbidities. This relation was statistically significant for most cognitive domains in adjusted models. Furthermore, the VACS Index predicted concurrent NCI beyond nadir CD4 and estimated duration of infection. Older age, lower hemoglobin, and lower CD4 counts were the VACS components most strongly linked to NCI. Conclusions: The findings extend previous research on the potential usefulness of the VACS Index in predicting HIV-associated outcomes to include NCI. Although the effect size was relatively small, our findings suggest that demographic information, HIVdisease factors, and common comorbidities might each play important roles in the clinical manifestation of cognitive impairment among HIV-infected individuals. Additional research is needed to determine if a more sensitive and specific index can be developed. Copyright © 2013 by Lippincott Williams and Wilkins.