High-volume systemic-to-pulmonary ductus arteriosus shunts in premature infants are associated with adverse neonatal outcomes. The role of an atrial communication (AC) in modulating the effects of a presumed hemodynamically significant patent ductus arteriosus (PDA) is poorly studied. The objective of this study was to characterize the relationship between early AC and echocardiographic indices of PDA shunt volume and clinical neonatal outcomes. A retrospective review of preterm infants (born at <32 weeks' gestation) who underwent echocardiography in the first postnatal week was performed. The cohort was divided into four groups on the basis of presence of a presumed hemodynamically significant PDA (≥1.5 vs <1.5 mm) and AC size (≤1 vs >1 mm), and echocardiographic measures of PDA shunt volume were then compared. Clinical outcomes, including chronic lung disease and intraventricular hemorrhage, were also compared among all four groups. A total of 199 preterm infants (mean birth weight, 928 ± 632 g; mean gestational age, 26.6 ± 1.5 weeks) were identified; 159 infants had PDAs ≥ 1.5 mm, of whom 52 had ACs ≤ 1 mm and 107 had ACs > 1 mm. The remaining 40 infants had PDAs < 1.5 mm, of whom 23 had ACs ≤ 1 mm and 17 had ACs > 1 mm. Infants with PDAs ≥ 1.5 mm and ACs > 1 mm had higher pulmonary vein D-wave velocities (P < .05), higher left ventricular output (P < .005), higher PDA scores (P < .001), and increased rates of reversed diastolic flow in the descending aorta (P < .001), celiac artery (P < .001), and middle cerebral artery (P < .001) than infants with either PDAs < 1.5 mm or PDAs ≥ 1.5 mm and ACs ≤ 1 mm. There was no difference in the incidence of intraventricular hemorrhage, but infants with PDAs ≥ 1.5 mm and ACs > 1 mm had a higher risk for a composite outcome of chronic lung disease or death before hospital discharge (P < .05). Echocardiographic evidence of ACs > 1 mm in patients with PDAs ≥ 1.5 mm during the first postnatal week may be a marker of a more pathologic hemodynamically significant PDA in premature infants. Future investigations should evaluate if early identification and treatment of patients with both high-volume PDAs and larger atrial-level communications may help mitigate adverse outcomes, such as chronic lung disease or death, in this high-risk patient population. Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.