HIV infection and the antiretroviral therapy (ART) used to treat it have been shown to increase cardiovascular disease (CVD) risk. In the past two decades, mortality trends in individuals with HIV show increasing CVD-related mortalities and decreasing AIDS-related mortalities. Studies have shown several health benefits in HIV-infected individuals who participate in regular physical activity (PA). PURPOSE: To investigate the associations between PA and several CVD risk factors in HIV-infected and uninfected women enrolled in the Women’s Interagency HIV Study (WIHS), a longitudinal cohort study examining the epidemiology of U.S. women living with and at risk for HIV. METHODS: Cross-sectional, secondary data analyses were completed on 496 WIHS participants from 6 sites (Bronx: n=91, Brooklyn: n=128, Chicago: n=35, District of Columbia: n=101, Los Angeles: n=116, San Francisco: n=25). Self-reported PA was assessed using an adaptation of the Physical Activity History questionnaire validated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Multivariate linear regression with backward selection models were used to assess the associations of PA with waist circumference, hemoglobin A1c, triglycerides, high-density lipoprotein cholesterol, and blood pressure (BP). Separate models were run for HIV-infected and uninfected women. Age, BMI, race, income, education, smoking, alcohol use, family history of CVD, viral load, CD4, and ART were investigated as covariates and included in the final model if the association was P≤0.10. Significance was defined as P≤0.05. RESULTS: Among all women, PA was associated with significantly reduced waist circumference (P=0.02); however, the interaction between PA and HIV was marginally significant (P=0.06). There was a significant interaction between PA and HIV on diastolic BP (P=0.04), where PA was inversely related to diastolic BP in HIV-infected women (P<0.01) and unrelated to diastolic BP in uninfected women (P=0.81). In addition, PA was associated with significantly lower systolic BP (P=0.01). CONCLUSIONS: These data suggest that PA is associated with a reduction in some CVD risk factors in HIV-infected women. Further research is needed to more fully examine the association between PA and CVD risk factors in individuals infected with HIV.