Background. The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer. Material and methods. Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors. Results. Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer. Discussion. The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.