Massive pulmonary hemorrhage (MPH) in newborn infants is a catastrophic event with a fatal result. The aim of this study was to assess the efficacy of high frequency oscillatory ventilation (HFOV) as a rescue therapy for MPH in newborn infants. Eighteen newborn infants with MPH refractory to conventional mechanical ventilation were treated with HFOV. Changes in oxygenation were assessed using arterial-alveolar oxygen tension ratio (a/APO2) and oxygenation index (OI) during HFOV. The most common underlying disorder of MPH was preterm patent ductus arteriosus (PDA). Thirteen out of 18 (72%) newborn infants with MPH responded to HFOV and survived. Five out of 18 (28%) did not respond to HFOV and died. There were no differences between responders and nonresponders in gestational age, birth weight, pre-HFOV OI, and age of MPH onset. In responders, there was a rapid increase in a/APO2 from 0.18+/-0.04 to 0.40+/-0.08 at 30 minutes after HFOV. There was also significant decrease in OI from 14.9+/-4.7 to 8.1+/-1.5 at 1 hour after HFOV. We conclude that HFOV shows rapid and dramatic improvements and has ultimately life-saving effects in MPH of newborn infants.