Objective: To evaluate the existence of an interaction between smoking habit and hypertension (HBP), diabetes (DBT), hypercholesterolemia (HC), hypertrygliceridemia (HTG) and hypoalphalipoproteinemia (Hypo-ALPHA) in determining carotid artery intima-media thickness (IMT) in patients attending a Lipid Clinic. Methods: Data from 1113 never-smokers (564 HBP, 34 DBT, 961 HC, 226 HTG, 159 Hypo-ALPHA patients), 377 former-smokers (208 HBP, 24 DBT, 301 HC, 110 HTG, 109 Hypo-ALPHA patients), 315 current-smokers (126 HBP, 13 DBT, 272 HC, 115 HTG, 102 Hypo-ALPHA patients) were analysed. Among the 692 former/current smokers, 435 were light-smokers (packyear<30) and 257 were heavy-smokers (packyear≥30). Results: Independent to the presence/absence of each vascular risk factor considered, carotid artery IMT was always higher in current-smokers, lower in former-smokers and lowest in never-smokers. Similarly, IMT was also always higher in heavy-smokers, lower in light-smokers and lowest in never-smokers. A significant interaction with smoking habits was found, however, only when hypertension (p=0.03) or diabetes (p=0.04) were considered. Conclusions: Smoking habit acts as an additional independent determinant of carotid IMT either in presence or absence of HC, HTG and Hypo-ALPHA. In view of the significant interaction with hypertension and diabetes, smoking cessation is particularly advisable in this kind of patients. Funding: Research described in this article was supported in part by Philip Morris USA Inc. and Philip Morris International.