OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors have become standard of care. RESEARCH DESIGN AND METHODS: All patients with type 2 diabetes and DN (n = 543) at the Steno Diabetes Center were followed during 2000-2010. GFR was measured yearly with 51Cr-EDTA plasma clearance. Annual decline in GFR was determined in patients with at least three measurements over a minimum of 3 years (∆GFR cohort, n = 286). Results were compared with historical data, obtained using identical criteria at our hospital, before implementation of current treatment guidelines. RESULTS: Baseline mean (SD) GFR was 74 (32) mL/min/1.73 m2. More than 93% received RAS inhibition. During median 7.8 (interquartile range 5.7-9.8) years, mean (SE) annual GFR decline was 4.4 (0.24) compared with previously 5.2 (0.27) mL/min/1.73 m2/year (P = 0.04). Doubling of plasma creatinine or end-stage renal disease (ESRD) developed in 19%, and 37% died during 5.7 (3.3-8.8) years. Mortality from onset of DN in the ∆GFR cohort was compared with that of our prior ∆GFR cohort from 1983 to 2003 (n = 227). Crude mortality risk was reduced by 42% and after age adjustment by 50% (P < 0.001 for both). In a multistate model accounting for competing risks of ESRD and death, prior cardiovascular disease and lower GFR were predictors of mortality, whereas albuminuria, HbA1c, and low GFR predicted ESRD. CONCLUSIONS: Overall prognosis has improved considerably with current multifactorial treatment of DN in type 2 diabetes, including long-term RAS inhibition.