Atrial fibrillation (AF) affects subjects with Chagas' disease and is an indicator of poor prognosis. We investigated clinical, echocardiographic and electrocardiographic variables of Chagas' disease in a long-term longitudinal study as predictors of a new-onset AF episode lasting >24 h, nonfatal embolic stroke and cardiac death. Fifty adult outpatients (34 to 74 years old, 62% females) staged according to the Los Andes classification were enrolled. During a follow-up of (mean +/- SD) 84.2 +/- 39.0 months, 9 subjects developed AF (incidence: 3.3 +/- 1.0%/year), 5 had nonfatal stroke (incidence: 1.3 +/- 1.0%/year), and nine died (mortality rate: 2.3 +/- 0.8%/year). The progression rate of left ventricular mass and left ventricular ejection fraction was significantly greater in subjects who experienced AF (16.4 +/- 20.0 g/year and -8.6 +/- 7.6%/year, respectively) than in those who did not (8.2 +/- 8.4 g/year; P = 0.03, and -3.0 +/- 2.5%/year; P = 0.04, respectively). In univariate analysis, left atrial diameter >= 3.2 cm (P = 0.002), pulmonary arterial hypertension (P = 0.035), frequent premature supraventricular and ventricular contraction counts/24 h (P = 0.005 and P = 0.007, respectively), ventricular couplets/24 h (P = 0.002), and ventricular tachycardia (P = 0.004) were long-term predictors of AF. P-wave signal-averaged ECG revealed a limited long-term predictive value for AF. In chronic Chagas' disease, large left atrial diameter, pulmonary arterial hypertension, frequent supraventricular and ventricular premature beats, and ventricular tachycardia are long-term predictors of AF. The rate of left ventricular mass enlargement and systolic function deterioration impact AF incidence in this population.