Meconium aspiration continues to be a major cause of morbidity and mortality in newborn infants and is one of the most common indications for extracorporeal membrane oxygenation. Lab studies have suggested that meconium inactivates surfactant and displaces surfactant from the alveolar surface. A recent report has suggested a clinical role for surfactant therapy in human infants with meconium aspiration. We evaluated the effect of surfactant (Survanta) lavage on a piglet model of meconium aspiration. Meconium pneumonitis was created by administration of 4 mL/kg of a 20% slurry of human meconium via endotracheal tube. Twenty-four newborn piglets were then randomly assigned to one of three groups: 1) suction only (n = 7), 2) saline lavage (n = 5), or 3) surfactant lavage (n = 7). Five piglets were excluded from analysis due to death from pneumothorax during meconium administration (n = 3), death from pneumothorax during saline lavage (n = 1), and death from pneumothorax during surfactant lavage (n = 1). The surfactant group had a statistically significant (p less than 0.05) improvement in arterial to alveolar oxygen ratio gradient versus both control groups for the first 3 h. The oxygenation index was statistically significant versus the suction only group at 1, 3, and 4 h. Surfactant lavage of meconium aspiration in piglets results in short-term improvement of oxygenation and warrants further study.