AIMS: Neopterin has emerged as a novel predictor of coronary events. The study aim was to compare the predictive value of neopterin and C-reactive protein (CRP) on long-term risk for fatal ischemic heart disease (IHD) in persons with newly diagnosed diabetes compared to persons without diabetes. METHODS AND RESULTS: In 1984-1986 a large population study, HUNT 1, was conducted in Norway. During the study, 205 patients were diagnosed with formerly unknown diabetes. A matched control group without diabetes was selected from the HUNT 1 population. Fatal IHD was registered until 2004. Blood samples were drawn at baseline and serum was analysed for neopterin and CRP. Cox regression analysis with correction for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios (HR) for fatal IHD. In the diabetes group, neopterin and CRP were independent predictors of fatal IHD, HR 2.59 (1.11-6.01) and 2.45 (1.05-5.69), respectively. Neither CRP nor neopterin were significant predictors of fatal IHD in the control group. CONCLUSION: In subjects with diabetes, both neopterin and CRP were independent predictors of fatal IHD, suggesting that these two markers reflect different aspects of the pathogenesis underlying fatal coronary events.