Background: Transforming growth factor-b1 (TGF-β1) may be implicated in the development of Chagas heart disease. However, the clinical value of TGF-β1 measurement is yet to be determined. Methods: We retrospectively analyzed the outcome of 54 Chagas disease patients without heart failure and with left ventricular (LV) ejection fraction .45% whose TGF-β1 serum values were determined between January 1998 and December 1999. Primary end point was all-cause mortality and secondary end point was the combination of all-cause mortality or hospitalization due to worsening heart failure or cardiac arrhythmias. Results: TGF-β1 was independently associated with the occurrence of the primary and secondary end points. The optimal cutoff for TGF-β1 to identify the primary end point was 12.9 ng/ml (area under the curve = 0.82, p = 0.004, sensitivity 100%, and specificity 57%) and to identify the secondary end point was 30.8 ng/ml (area under the curve = 0.72, p = 0.03, sensitivity 60%, and specificity 86%). LV ejection fraction and LV end-diastolic diameter were also independent predictors of the primary and secondary endpoints, respectively. Conclusion: The described association between TGF-β1 and clinical outcome provides evidence towards the clinical value of TGF-β1 in Chagas disease.