The systemic right ventricle (RV) in congenital heart disease is susceptible to progressive dilation and dysfunction. A 2-dimensional echocardiographic means for serial monitoring of the RV would be of great value in this clinical setting. We used 2-dimensional echocardiography with knowledge-based reconstruction (2DE-KBR) for evaluation of systemic RV. Patients with d-transposition of great arteries repaired with an atrial switch and without implanted pacemakers were prospectively recruited for same-day 2DE-KBR and cardiac magnetic resonance (CMR) imaging. RV images were acquired in various 2-dimensional imaging planes using a 3-dimensional space–localizing device attached to the imaging transducer and 3-dimensional reconstruction was performed. RV end-diastolic volume, end-systolic volume, and ejection fraction (EF) were calculated and compared to volumetric CMR analysis. Fifteen patients (7 women, 8 men, 24 ± 7 years old, weight 67 ± 12 kg) were studied. There was good agreement of 2DE-KBR and CMR measurements. Mean RV end-diastolic volume was 221 ± 39 ml with 2DE-KBR and 231 ± 35 ml with CMR (r = 0.80); mean end-systolic volume was 129 ± 35 ml with KBR and 132 ± 30 ml with CMR (r = 0.82), and EF was 42 ± 10% with KBR and 43 ± 7% with CMR (r = 0.86). For 2DE-KBR mean interobserver variabilities were 4.6%, 2.6%, and 4.3%; intraobserver variabilities were 3.2%, 3.1%, and 2.3%, respectively, for end-diastolic volume, end-systolic volume, and EF. In conclusion, this study demonstrates the clinical feasibility of quantifying systemic RV volumes and function using 2DE-KBR in adolescents and young adults with repaired d-transposition of great arteries and good agreement of measurements with CMR.