Tobacco and alcohol consumption are strongly related to other cardiovascular and cancer risk factors. The aim of the present study was to analyse the association of nutrient intake, blood lipid variables and leisure-time physical activity with tobacco and alcohol consumption status. Participants were recruited in a cross-sectional population-based survey, including cardiovascular risk factor measurements and evaluation of physical activity and diet intake in a Mediterranean population (n 1748). Multiple linear regression analysis, adjusted for several confounders, showed a direct association of saturated fatty acids (g and % total energy intake), dietary cholesterol intakes and serum triacylglycerol with smoking. An inverse association was observed for smoking and unsaturated fatty acids (% energy intake), vitamin C, alpha-tocopherol and beta-carotene intakes, leisure-time physical activity and HDL-cholesterol. These associations were not observed for alcohol drinking. After adjusting for the confounders earlier mentioned, low dietary intakes of vitamin C and dietary fibre were more likely in heavy-smokers as compared with non-smokers (odds ratio 1.74 (95 % CI 1.07, 2.73) and 1.94 (95 % CI 1.29, 2.92) of low vitamin C (<60 mg/d) and dietary fibre intakes (<10 g/d) respectively). Alcohol consumption was directly associated with HDL-cholesterol and triacylglycerol, and attenuated the effects of smoking on HDL-cholesterol. These results suggest that the dietary intake of fibre and several antioxidant components of the Mediterranean diet is reduced in smokers, who also show an adverse lipid profile. However, the worst triacylglycerol levels are associated with the combination of heavy smoking and heavy alcohol drinking. Moderate alcohol consumption was not associated with an unhealthy diet pattern or adverse lipid profile. The health benefits of the Mediterranean diet appear to be strongly counteracted by smoking.