Homocysteine levels are considered, by some investigators, as an independent factor of cardiovascular disease; however, others suggest that there is not a causal relationship. The aim of this work was to investigate the associations between homocysteine levels and several lifestyle-related factors. The ATTICA study is a population-based cohort that has randomly enrolled 1128 adult men and 1154 women, stratified by age and gender, from the greater area of Athens, during 2001-2002. Among several demographic, lifestyle, clinical and biochemical characteristics, we measured total plasma homocysteine levels. For the present analysis, we excluded people who had a history of cardiovascular disease. The factors that showed the strongest relationship with homocysteine levels, in both genders, even after adjusting for several potential confounders were: cigarette smoking (p = 0.03), endurance exercise (inverse, p < 0.05), fruit (inverse, p = 0.01) and vegetable intake (inverse, p = 0.04), and alcohol (p = 0.04) and coffee intake (p = 0.04). In conclusion, several lifestyle-related factors seem to be associated with homocysteine levels. However, the vast majority of the associations were weak when we adjusted for other co-factors. The latter may indicate the mutual confounding effect of various socio-demographic, anthropometric and other clinical characteristics on the relationship between homocysteine and cardiovascular risk.