Wave separation analysis (WSA) reveals the impact of forward- and backward-running waves on the arterial pressure pulse, but the calculations require a flow waveform. This study investigated (1) the variability of the ascending aortic flow waveform in children and adolescents with/without a childhood heart disease history (CHD); (2) the accuracy of WSA obtained with a representative flow waveform (RepFlow), compared with the triangulation method and published ultrasound-derived adult representative flow; (3) the impact of limitations in Doppler ultrasound on WSA; and (4) generalizability of results to adults with a history of CHD. Phase contrast MRI was performed in youth without (n = 45, Group 1, 10–19 years) and with CHD (n = 79, Group 2, 7–18 years), and adults with CHD history (n = 29, Group 3, 19–59 years). Segmented aortic cross-sectional area was used as a surrogate for the central pressure waveform in WSA. A subject-specific virtual Doppler ultrasound was performed on MRI data by extracting velocities from a sample volume. Time/amplitude-normalized ascending aortic flow waveforms were highly consistent amongst all groups. WSA with RepFlow therefore yielded errors < 10% in all groups for reflected wave magnitude and return time. Absolute errors were typically 1.5–3 times greater with other methods, including subject-specific (best-case/virtual) Doppler ultrasound, for which velocity profile skewing introduced waveform errors. Our data suggest that RepFlow is the optimal approach for pressure-only WSA in children and adolescents with/without CHD, as well as adults with CHD history, and may even be more accurate than subject-specific Doppler ultrasound in the ascending aorta.