To investigate the effect of breath-holding on left-to-right shunts in patients with a secundum atrial septal defect (ASD). Thirty-five consecutive patients with secundum ASDs underwent right heart catheterization and invasive oximetry. Phase-contrast magnetic resonance imaging (MRI) was performed for the main pulmonary artery and ascending aorta. All measurements were obtained during free breathing (FB) (quiet breathing; no breath-hold), expiratory breath-hold (EBH), and inspiratory breath-hold (IBH). Pulmonary circulation flow (Qp) and systemic circulation flow (Qs) were calculated by multiplying the heart rate by the stroke volume. Measurements during FB, EBH, and IBH were compared, and the differences compared to invasive oximetry were evaluated. There were significant differences among the measurements during FB, EBH, and IBH for Qp (FB, 7.70 ± 2.68; EBH, 7.18 ± 2.34; IBH, 6.88 ± 2.51 l/min); however, no significant difference was found for Qs (FB, 3.44 ± 0.74; EBH, 3.40 ± 0.83; IBH, 3.40 ± 0.86 l/min). There were significant differences among the measurements during FB, EBH, and IBH for Qp/Qs (FB, 2.38 ± 1.12; EBH, 2.24 ± 0.95; IBH, 2.14 ± 0.97). Qp/Qs during FB and EBH correlated better with Qp/Qs measured by invasive oximetry than did IBH. The limit of agreement was smaller for EBH than for FB and IBH. In patients with secundum ASDs, Qp/Qs significantly decreased with breath-holding. The accuracy of the Qp/Qs measurement by MRI compared with invasive oximetry during EBH was higher than during FB and IBH.