Preterm triplets were treated with calf lung surfactant extract (CLSE). Two were treated at birth without development of respiratory distress syndrome (RDS); one was treated after development of RDS, with rapid improvement. These cases demonstrated the efficacy of exogenous surfactant and the potential benefit of prophylaxis (early treatment) over late treatment. Although various exogenous surfactants have been used successfully to treat or prevent RDS in preterm infants, the optimal time of surfactant treatment has not been established. Surfactant therapy at birth results in a reduction in the incidence and severity of RDS, but it could lead to unnecessary treatment in a significant portion of patients. On the other hand, delaying treatment is likely to lessen the benefits of exogenous surfactant by various factors, including barotrauma and oxygen toxicity. The triplets in this report were treated with Infasurf CLSE. Two were treated at birth without development of RDS, but one was treated after development of RDS, with rapid improvement of respiratory status.