Abstract Extracorporeal lung support (ECLS) for newborns with acute respiratory failure has achieved increased popularity over the last decade. However, precise criteria for its implementation remain controversial. The aim of this study was to assess the value of Doppler echocardiography (DE) in 31 neonates with Pao 2 of ≤ 50 mmHg, FIO 2 of 1, and optimal ventilation. Treatment included mechanical ventilation, paralysis, volume loading, vasopressors, and tolazoline. Markers indicative of ECLS (failure of maximal medical therapy, assessed by AaDO 2 of more than 610 mm Hg beyond 8 hours and/or an oxygenation index (OI = mean airway pressure × FIO 2%/postductal Pao 2) of more than 40 beyond 4 to 6 hours) were present in 23 (group 1) and absent in eight (group 2). Shunt direction and systolic pulmonary arterial pressure (sPAP) calculated from tricuspid insufficiency velocity were assessed using DE. At the time of admission, sPAP was significantly higher in group 1 (62.1 v 43.7 mm Hg). On day 1, group 1 differed from group 2 in maximum sPAP value (73.2 v 44.4 mm Hg), Paco 2 (56.1 v 40 mm Hg), right-to-left shunting (85% v 25% of the patients), and pulmonary-to-systemic-pressure systolic ratio (sPAP:sSAP) (1.29 v 0.75). Patients with an sPAP:sSAP ratio of more than 1 and patients with high sPAP associated with high PaCO 2 on day 1, all later (average, 10 hours later) fulfilled ECLS criteria; this suggests that DE assessment of pulmonary circulation may yield early and predictive markers of impending ECLS indication. Further confirmation of these results would help avoid unecessary delays in ECLS implementation in newborns with severe respiratory failure.