We assessed the relationship between positive affect and viral suppression among women with HIV infection. Three waves of 6-month data were analyzed from 995 women on HIV antiretroviral therapy participating in the Women's Interagency HIV Study (10/11-3/13). The predictor variable was self-reported positive affect over 2 waves of data collection, and the outcome was suppressed viral load, defined as plasma HIV-1 RNA <200 copies/mL, measured at a third wave. Women with higher positive affect (36%) were more likely to have viral suppression at a subsequent wave (OR 1.92, 95% CI [1.34, 2.74]). Adjusting for covariates and their interactions, including negative affect, Wave 1 viral suppression, adherence, study site, recruitment cohort, substance use, heavy drinking, relationship status, interpersonal difficulties, and demographics, a statistically significant interaction was detected between negative affect, positive affect and viral suppression, t(965) = -2.7, p = .008. The association of positive affect and viral suppression differed at negative affect quartile values. For those reporting no negative affect, the AOR for positive affect and viral suppression was 2.41 (95% CI [1.35, 4.31]); at a negative affect score of 2, the AOR was 1.44 (95% CI [0.87, 2.36]); and at a score of 5.5, the AOR was 0.58 (95% CI [0.24, 1.42]). Our central finding related to the interaction effect, that positive affect is associated with viral control under conditions of lower negative affect, is consistent with previous theory and research with other health outcomes, and can help guide efforts to further delineate mechanisms linking affect and health. (PsycINFO Database Record