Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk patients with T2DM. Methods and Results Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT-proBNP alone and with NT-proBNP added, using C-statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6-year follow-up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT-proBNP alone was as discriminatory as the base model for predicting death (C-statistic, 0.745 versus 0.744, =0.95) and the cardiovascular composite outcome (C-statistic, 0.723 versus 0.731, =0.37). When NT-proBNP was added, it increased the predictive ability of the base model for death (C-statistic, 0.779 versus 0.744, <0.001) and for cardiovascular composite outcome (C-statistic, 0.763 versus 0.731, <0.001). Conclusions In high-risk patients with T2DM, NT-proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00549757.