Background: Cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in HIV-infected adults. Research in noninfected populations suggests that knowledge of CVD risk factors significantly influences perception of risk. Understanding the level of risk factor knowledge and risk perception can inform the development of innovative interventions to reduce risk. The purpose of this study was to describe cardiovascular risk factor knowledge and risk perception in a cohort of HIV-infected adults. Specific aims included (a) describing the estimated risk of CVD, the perceived risk of CVD, and the level of CVD risk factor knowledge; (b) describing the relationship between estimated and perceived risk, and (c) examining the influence of risk factor knowledge on perceived risk of CVD. The Health Belief Model was the theoretical framework that guided the study. Methods: A prospective observational cohort; cross-sectional design. A convenience sample of 130 HIV-infected adults was recruited from two hospital-based HIV clinics. Each participant had one study visit in which all data were collected by direct interview. Results: Results: Mean age of enrollees was 48 years (SD 8.4); 62% were male; 41.5% White, 32% Black, 23% Hispanic; 56% current smokers; mean years since HIV diagnosis were 14.7; mean BMI 27 (SD 5.5); 48.5% had prehypertension. Higher scores on the Heart Disease Fact Questionnaire indicate a higher degree of knowledge. In this sample, the Mean was 19, (S.D. 3.5; range 6–25), indicating a fair degree of knowledge. Estimated and perceived risk were significantly, though weakly, correlated r (126) = .24, p = .01. Controlling for age, risk factor knowledge was not predictive of perceived risk (F[1,117] = 0.13, p > .05). Conclusions: HIV-infected adults are at increased risk for cardiovascular disease. Traditional CVD risk factors such as smoking, prehypertension, and being overweight are highly prevalent. Despite having a fair level of risk factor knowledge, knowledge did not influence perception of risk for CVD. Research to improve risk perception and to develop innovative interventions that reduce CVD risk is needed for this population.