• Since the initial description of persistent pulmonary hypertension of the newborn (PPHN), the management of these infants has been controversial. A variety of therapeutic modalities, such as extracorporeal membrane oxygenation, have been utilized. Early recognition of a group of patients with PPHN who might require aggressive therapy would be clinically useful. Highest alveolar-arterial oxygen gradient at or near diagnosis was evaluated retrospectively in 53 patients with PPHN in relation to survival, aggressiveness of management, and frequency of pulmonary complications (air leak and bronchopulmonary dysplasia). Highest alveolararterial oxygen gradient was a good early predictor of nonsurvival and was significantly higher in nonsurvivors compared with survivors (mean [±SD], 618±23 mm Hg vs 521 ±128 mm Hg). Values of 600 mm Hg or greater were more frequent in the nonsurvivors compared with the survivors (92% vs 37%). Air leak also proved to be a good predictor of nonsurvival.