Purpose: Some centers including ours have used glutaraldehyde-treated pericardium for reconstruction of coronary button defects at the arterial switch operation (ASO). This may impact the incidence of pulmonary stenosis and prevent primary closure of the pericardium. We report a series where 2-ply extracellular matrix (Tyke) was used to reconstruct the neopulmonary root. Methods: Since May 2016, all patients (n = 38) were repaired using Tyke for reconstruction of the coronary button defects. We measured the incidence of pulmonary stenosis and insufficiency at the main pulmonary artery (MPA) and branch pulmonary arteries by echocardiogram and compared these measurements with the historical cohort where pericardium (some treated with glutaraldehyde, some fresh) was used. Results: Mean follow-up was 3.0 ± 2.4 years (range, 1 month to 8 years). The mean gradient at the neopulmonary valve was 6.8 ± 7 mm Hg in the Tyke group versus 23.7 ± 16.1 in the pericardium group (P < .01). The mean gradient at the distal MPA was 8.9 ± 2.9 mm Hg for the Tyke group and 44.5 ± 40.1 in the historical group (P < .01). The mean gradient at the proximal left and right branch pulmonary arteries was 29 ± 19 and 32 ± 16 mm Hg in the Tyke group and 33 ± 16 and 36 ± 26 (NSD). At the last follow-up, six of 38 patients (18%) in the Tyke group had a pulmonary reintervention: five patients had a balloon dilation of branch pulmonary arteries, and one patient had dilation of the MPA. No patients underwent surgical intervention on the pulmonary valve or the reconstructed MPA. Conclusion: Tyke is a reasonable alternative material for reconstruction of the coronary button defects during the ASO within the follow-up period.