Patients with repaired tetralogy of Fallot have a reduced percentage of predicted peak oxygen consumption (VO(2)) and percentage of oxygen pulse (O(2)P%) compared to healthy controls. Because data regarding the progression of exercise intolerance in these patients is limited, we sought to analyze the serial exercise data from patients with Tetralogy of Fallot to quantify the changes in their exercise capacity over time and to identify associations with clinical and cardiac magnetic resonance imaging variables. The data from cardiopulmonary exercise tests (CPXs) from 2002 to 2010 for patients with repaired tetralogy of Fallot with ≥2 CPXs separated by ≥12 months were analyzed. Tests occurring after interventional catheterization or surgery were excluded. A total of 70 patients had 179 CPXs. They had a median age at the initial study of 23.6 years and an interval between the first and last CPX of 2.8 years. At the initial CPX, the peak VO(2) was 27.6 ± 8.8 ml/kg/min (78 ± 19% of predicted), and the peak O(2)P% was 89 ± 22% of predicted. At the most recent study, the peak VO(2) averaged 25.0 ± 7.4 ml/kg/min (73 ± 16% of predicted), and the peak O(2)P% averaged 83 ± 20% (p <0.01) for each versus the initial CPX. The decrease in the peak VO(2) was strongly associated with a decrease in O(2)P% and an increase (worsening) in the slope of the minute ventilation-versus-carbon dioxide production relation. Changes in the peak VO(2) did not correlate with concomitant changes in any other CPX variable. The rate of decrease was not related to a history of shunt palliation, age at CPX, or any other baseline clinical parameter, including cardiac magnetic resonance measurements. In conclusion, the exercise capacity of patients with repaired tetralogy of Fallot tends to decrease over time. This deterioration is variable and unpredictable and is primarily related to a decrease in the forward stroke volume at peak exercise., (Copyright © 2011 Elsevier Inc. All rights reserved.)