Positive affect has been shown to be associated with a number of positive health outcomes, although data on the relationship between positive affect and health in the context of HIV infection has been mixed. In this study, the relationship between positive affect over a one year period and HIV RNA viral load suppression six months following the one year observation period are examined among 933 women participating in a longitudinal cohort study designed to assess the natural and treated history of HIV infection in women. This analysis indicates that high positive affect is associated with an increased likelihood of undetectable HIV RNA viral load, and that this relationship remains statistically significant after controlling for behavioral factors such as HIV antiretroviral adherence, substance use, negative affect, interpersonal difficulties, and somatic issues. These findings suggest that interventions designed to promote positive affect may be an important adjunct to interventions designed to improve disease outcomes among women living with HIV.