Patients with previous Fontan surgery have reduced peak oxygen consumption (Vo 2), and data regarding progression of exercise intolerance is limited. The purpose of this study was to assess the evolution of exercise tolerance in patients with previous Fontan surgery. We performed a retrospective cohort study of patients with previous Fontan surgery who underwent cardiopulmonary exercise testing between November 2002 and January 2009. Patients were required to have completed at least two tests, with adequate levels of effort, >or-6 months apart. We identified 78 patients (55% male) who had undergone a total of 215 cardiopulmonary exercise tests. Age at initial study was 19.7 +/- 10.2 years; time interval since previous Fontan surgery 13.3 +/- 5.7 years; and time interval between the initial and the most recent exercise test was 3.0 +/- 1.4 years. Morphologic left ventricle was present in 58 (74.4%) patients. At baseline, peak Vo 2 averaged 24.7 +/- 7.0 ml/kg/min (63.7% +/- 15.8% predicted). At most recent study, peak Vo 2 averaged 23.2 +/- 7.2 ml/kg/min, (60.4% +/- 13.9% predicted). Percent predicted peak Vo 2 declined slowly, with a mean rate of decline of 1.25 +/- 0.36 percentage points/y (p < 0.001). Most of the decline occurred in patients < 18 years of age (mean rate of decline 1.78 +/- 0.46 percentage points/y; p = 0.0004). Thereafter, the rate of decline was less marked (mean rate of decline 0.54 +/- 0.57 percentage points/y; p = not significant). Ventricular morphology, type of Fontan procedure, and cardiac medications were not predictive of progressive exercise intolerance. In conclusion, although the exercise function of previous Fontan patients tends to decline during late adolescence, it appears to stabilize during early adulthood.