OBJECTIVE We investigated endotrophin, a profibrotic signaling molecule reflecting collagen VI formation, in serum and urine as risk marker for complications to type 2 diabetes. RESEARCH DESIGN AND METHODS Endotrophin was measured in 774 individuals with type 2 diabetes. Outcomes included a composite kidney end point, first major adverse cardiovascular event (MACE), mortality, progression of albuminuria, incident heart failure, and sight-threatening eye disease. Adjusted Cox proportional hazards models were applied. RESULTS Doubling of serum endotrophin was associated with the kidney end point (n 5 49; hazard ratio 1.80 [95% CI 1.13–2.87]), first MACE (n 5 66; 1.54 [1.04–2.28]), mortality (n 5 156; 1.69 (1.31–2.19]), and incident heart failure (n 5 42; 1.63 [1.02–2.60]). A doubling of urine endotrophin was associated with progression of albuminuria (n 5 85; 1.20 [1.04–1.39]). CONCLUSIONS Serum endotrophin was a risk marker for mortality and kidney and cardiovascular complications in type 2 diabetes. Urine endotrophin was a marker for albu-minuria progression.