Abstract: Background Diabetes mellitus (DM) and chronic kidney disease (CKD) are well-known cardiovascular and mortality risk factors. To what extent they act in an additive manner and whether the etiology of CKD modifies the risk is uncertain. Methods The multicenter, prospective, observational German Chronic Kidney Disease study comprises 5217 participants (1868 with DM) with a baseline mean estimated glomerular filtration rate of 30-60 mL/min/1.73 m2 and/or proteinuria >0.5 g/day. We categorized patients whose CKD was caused by cardiovascular or metabolic diseases (CKDcvm) with and without DM, as opposed to genuine CKD (CKDgen) with and without DM. Recorded outcomes were first events of non-cardiovascular and cardiovascular death, 4-point major adverse cardiovascular events (4-point MACE) and hospitalization for heart failure (HHF). Results During the 6.5-year follow-up 603 (12%) non-cardiovascular and 209 (4%) cardiovascular deaths, 645 (12%) 4-point MACE, and 398 (8%) HHF were observed, most frequently in patients with DM having CKDcvm. DM increased the risk of non-cardiovascular [hazard ratio (HR) 1.92; 95% confidence interval (CI) 1.59-2.32] and cardiovascular (HR 2.25; 95% CI 1.62-3.12) deaths, 4-point MACE (HR 1.93; 95% CI 1.62-2.31) and HHF (HR 1.87; 95% CI 1.48-2.36). Mortality risks were elevated by DM to a similar extent in CKDcvm and CKDgen, but for HHF in CKDcvm only (HR 2.07; 95% CI 1.55-2.77). In patients with DM, CKDcvm (versus CKDgen) only increased the risk for HHF (HR 1.93; 95% CI 1.15-3.22). Conclusions DM contributes to cardiovascular and mortality excess risk in patients with moderate to severe CKD in both, CKDcvm and CKDgen. Patients with DM and CKDcvm are particularly susceptible to HHF