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To investigate the effects of aging and smoking on carotid intima–media thickness (cIMT) among patients with and without HIV.Data from a community sample of HIV-infected and HIV-uninfected participants were analyzed. Carotid intima–media thickness was measured via carotid ultrasound and smoking history was obtained via patient interview.Data on 166 male and female participants with stable HIV-infection and 152 healthy HIV-uninfected participants were analyzed. Among the HIV-infected and HIV-uninfected participants, a significant association was observed between age and cIMT [r = 0.51, P < 0.0001 (HIV), r = 0.39, P < 0.0001, (non-HIV)], and between smoking burden and cIMT [r = 0.42, P < 0.0001 (HIV), r = 0.24, P = 0.003 (non-HIV)]. In multivariate regression modeling among all participants (HIV and non-HIV), a significant three-way interaction was observed between age, smoking burden, and HIV status with respect to cIMT (P < 0.010), controlling for sex, race, and traditional cardiovascular disease (CVD) risk factors, such that increased cIMT was associated with increased smoking burden and age to a greater degree among HIV-infected vs. HIV-uninfected participants. Among HIV-infected participants a significant interaction between smoking burden and age with respect to cIMT was seen (P = 0.027) controlling for race, sex, CVD risk factors, immunological function, and antiretroviral therapy use.A significant interaction between HIV, age, and smoking on cIMT was observed, suggesting that HIV-infection modifies the relationship of age and smoking on cIMT in this population. These findings emphasize the need to encourage smoking cessation in this population, due to its deleterious effect on subclinical atherosclerosis in older HIV-infected patients.