End-tidal CO
2
(ET
CO
2
) monitoring and transcutaneous (TC) CO
2
monitoring were prospectively compared in 53 patients, 1 month to 16 years of age, with congenital heart disease (CHD). There were 32 patients with cyanotic CHD and 21 with acyanotic CHD. The TC-Pa
CO
2
difference was 2 ± 1 mm Hg and the ET-Pa
CO
2
difference was 5 ± 3 mm Hg (
P
< .0001). The TC-Pa
CO
2
difference was≤2 mm Hg in 30 of 53 patients and≤5 mm Hg in 53 of 53 patients. The ETPa
CO
2
difference was≤2 mm Hg in 9 of 53 patients and≤5 mm Hg in 30 of 53 patients (
P
< .001). No variation in the TC-Pa
CO
2
difference was noted based on the type of CHD (acyanotic vs cyanotic) or age. The ET-Pa
CO
2
difference was greater in patients with cyanotic versus acyanotic CHD (7 ± 3 mm Hg vs 4 ± 2 mm Hg,
P
< .0001) and in patients≤1 year of age versus patients ≥1 year of age (6 ± 3 mm Hg vs 4 ± 2,
P
= .008). In infants and children with CHD, TC monitoring provides a more accurate estimation of Pa
CO
2
than ET monitoring.