To evaluate the impact of a recently developed, non-invasive risk score predictive for type 2 diabetes on the incidence and mortality of cardiovascular diseases and specific types of cancer. A total of 23,455 participants from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study aged 35-65 years and free of diabetes and major chronic diseases at baseline (1994-1998) were followed through 2006 for incident myocardial infarction, stroke, types of cancer, and death. Risk score points were assigned to each participant based on age, waist circumference, height, physical activity, history of hypertension, smoking, alcohol consumption, and intake of red meat, whole-grain bread, and coffee. Hazard ratios (HRs) were estimated by Cox regression models. In age- and sex-adjusted analyses, participants with a high risk score (5-year probability to develop diabetes > or = 10%) had significantly higher risks of myocardial infarction (HR 2.7, 95% CI 1.5-5.0) and stroke (1.9, 1.0-3.6), but not of colon, breast or prostate cancer incidence, than those with a low score (5-year probability < 1%). In addition, participants with a high risk score had considerably higher risks of cardiovascular (HR 4.6, 95% CI 2.3-9.4), cancer (1.7, 1.1-2.7), and total mortality (2.4, 1.8-3.4), the latter being equivalent to a difference in life expectancy of 13 years. These data indicate that a risk score predictive for type 2 diabetes is also related to elevated risks of myocardial infarction, stroke, and premature death in apparently healthy individuals and emphasize the need for early intervention in high-risk individuals.