This study aimed to explore the relationship of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with cognition in women with (HIV+) and without HIV (HIV-) infection. One thousand six hundred ninety participants (1,196 HIV+, 494 HIV-) in the Women's Interagency HIV Study (WIHS) with data available on anthropometric measures comprise the analytical sample. Cross-sectional analyses using linear regression models estimated the relationship between anthropometric variables and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, Wide Range Achievement Test score, CD4 count, insulin resistance, drug use, and race/ethnicity. Among HIV+ women, BMI < 18.5 kg/m(2) was associated with poorer cognitive performance evidenced by longer Trails A and Trails B and shorter SDMT completion times. An obese BMI (30 kg/m(2) or higher) was related to better performance on Trails B and worse performance on the Stroop interference test. Among HIV- women, an obese BMI was related to worse performance on the Stroop color naming test. Few and inconsistent associations were observed between WC, WHR, and cognition. Among women at mid-life with chronic (at least 10 years) HIV infection, common anthropometric measures, primarily BMI, were differentially related to cognitive test performance by cognitive domain. Higher levels of BMI were associated with better cognitive function. In this era of antiretroviral therapies, restoration of health evidenced as higher BMI due to effective antiretroviral therapies, may improve cognitive function in middle-aged HIV-infected women.