BACKGROUND: The present study examines the association between carotid and coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus (HIV)-infected adults. METHODS: We measured the common and internal carotid intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured coronary artery calcium (CAC) using high-resolution, electrocardiographic, synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic syndrome was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. We compared the c-IMT measurements and CAC scores of patients with metabolic syndrome with the scores of those without metabolic syndrome using a Wilcoxon test for continuous variables and a chi2 test for categorical variables. To examine the association between surrogate markers and metabolic syndrome, we used logistic regression analysis. RESULTS: Participants with metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%; P=.15). Any positive CAC score was more likely to occur for participants with metabolic syndrome (80.3% vs. 46.7%; P<.0001). In a multivariate model adjusted for sex, age, ethnicity, and smoking status, participants with metabolic syndrome were more likely than those without metabolic syndrome to have an abnormal common c-IMT measurement (odds ratio [OR], 2.9; P=.020) and detectable CAC scores (OR, 4.9; P<.0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255). CONCLUSION: Our study demonstrates that HIV-infected individuals with metabolic syndrome may be at increased risk for subclinical atherosclerosis and supports screening for metabolic syndrome among HIV-infected patients at risk for cardiovascular disease.