OBJECTIVE:To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk. DESIGN:Cross-sectional analysis within the Hawaii Aging With HIV Cohort. METHODS:We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses. RESULTS:Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores. CONCLUSIONS:IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.