Background In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline. Methods Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP >45.2 ng/L and/or CAC ≥400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median). Results High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31). Conclusions In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.