Abstract We investigated the association between cardiac factors, spirometry, and exercise testing in patients with tetralogy of Fallot (TOF). Clinical data from patients with TOF performing a cardiopulmonary exercise test (CPET) was collected retrospectively over a 10-year period. 122 patients with TOF were identified, 52 excluded for incomplete exercise, spirometry, or cardiac data for 70 total patients included in the study. There was a male predominance 39 (56%), a mean age of 25 ± 12 years, with 28 (40%) < 18 years of age. The mean number of cardiac surgeries was 2.1 ± 1.2. Most, 46 (69%) had moderate to severe pulmonary valve insufficiency (PI) and 34 (51%) had moderate to severe right ventricular (RV) dilation. Mean forced vital capacity (FVC) was low at 81.8% predicted, and 32 (46%) with low FVC (< 80% predicted). Overall peak VO 2 /kg was low with a mean of 58.2 ± 13.2 % predicted. Using multiple regression analysis, a higher number of cardiac surgeries was an independent predictor of lower FVC ( p = 0.01). Lower FVC was itself an independent predictor of lower peak VO 2 /kg and O 2 pulse ( p < 0.05). Moderate or severe RV systolic dysfunction was an independent predictor of stroke volume response ( p = 0.03). Higher body mass index (BMI) was an independent predictor of all exercise measures being worse ( p < 0.05). Low FVC and reduced exercise capacity were common in our population of TOF patients. Low FVC was predictive of low exercise capacity while, of the cardiac measures only RV systolic dysfunction was significant and predictive of stroke volume response. Spirometry may be a valuable screening tool in evaluation of TOF patients.