The association between classical cardiovascular risk factors, including diet, and the 25-year incidence of non-insulin-dependent diabetes mellitus was examined in 841 middle-aged men within the Zutphen Study. The incidence rate was 3.8/1,000 person-years. In univariate analyses, baseline measurements of subscapular and tricipital skinfold thicknesses, body mass index (weight (kg)/height (m)2), cigarette use, resting heart rate, and systolic blood pressure were significantly associated with diabetes incidence. In multivariate survival analyses also taking age, energy intake, and alcohol consumption into account, subscapular skinfold thickness, resting heart rate, and cigarette use were independently related to diabetes incidence. The effect of subscapular skinfold thickness was shown among subjects free of cardiovascular disease at baseline and during follow-up and among cases who developed cardiovascular disease. Cigarette smoking was an independent risk factor only in men who remained free of cardiovascular disease, while the effect of resting heart rate was stronger within incident cases of cardiovascular disease. No associations were found between dietary factors and diabetes incidence.