Abstract Introduction: Vegetables and fruits have long been considered as conducive to cancer prevention, but this view has recently been challenged. We investigated the relation of vegetable and fruit intake with total cancer occurrence in the population-based cohort of the Greek component of the European Prospective Investigation into Cancer and nutrition (EPIC), which is characterized by high consumption of these foods. Materials and Methods: For a median of 7.9 years, 25,623 participants (10,582 men, 15,031 women) were actively followed-up, contributing 188,042 person-years. Cancer at any site was diagnosed in 851 participants (421 men, 430 women). Dietary intakes were ascertained at enrollment through an extensive, validated, interviewer-administered food frequency questionnaire. Data were analyzed through Cox regression, controlling for potential confounders. Results: An inverse association of cancer incidence with vegetables and fruits (mutually adjusted) was noted, reaching statistical significance for vegetables among women. When vegetables and fruits were combined, the inverse association with cancer occurrence was statistically significant for the entire cohort [hazard ratio per increasing quintile, 0.94; 95% confidence interval (95% CI), 0.88-0.99], as well as among women (hazard ratio per increasing quintile, 0.90; 95% CI, 0.83-0.98), but not among men (hazard ratio per increasing quintile, 0.95; 95% CI, 0.87-1.04). Conclusions: In a general population-based Greek cohort, we have found evidence that consumption of vegetables and fruits is inversely associated with incidence of cancer overall, although the associations seem to be weaker than expected on the basis of case-control studies previously undertaken in Greece. (Cancer Epidemiol Biomarkers Prev 2008;17(2):387–92)