Background and Purpose—Previous case– control studies have suggested a causal link between Chagas disease, which is caused by the protozoan Trypanosoma cruzi, and stroke. We investigated the relationship between Chagas disease and long-term stroke mortality in a large community-based cohort of older adults. Methods—Participants were 1398 (80.3% from total) residents aged _60 years in Bambuí City, Brazil. The end point was death from stroke. Potential confounding variables included age, sex, conventional stroke risk factors, and high sensitive C-reactive protein. Results—Participants of this study were followed from 1997 to 2007 leading to 9740 person-years of observation. The baseline prevalence of T. cruzi infection was 37.5% and the overall mortality rate from stroke was 4.62 per 1000 person-years. The risk of death from stroke among T. cruzi-infected participants was twice that of those noninfected (adjusted hazard ratio, 2.36; 95% CI, 1.25 to 4.44). A B-type natriuretic peptide level in the top quartile was a strong and independent predictor of stroke mortality among those infected (adjusted hazard ratio, 2.72; 95% CI, 1.25 to 5.91). The presence of both a high B-type natriuretic peptide level and electrocardiographic atrial fibrillation increased the risk of stroke mortality by 11.49 (95% CI, 3.19 to 41.38) in these individuals. Conclusions—This study provides new evidence supporting a causal link between Chagas disease and stroke. The results also showed that B-type natriuretic peptide alone or in association with atrial fibrillation has prognostic value for stroke mortality in T. cruzi chronically infected older adults