The leading treatments for premature infants suffering from respiratory distress syndrome (RDS) include 1) intratracheal instillation of lung surfactants, and 2) nasal continuous positive air pressure (nCPAP). Both approaches have shown clinical promise. An ideal therapy would combine the benefits of lung surfactant treatment and nCPAP (i.e., no intubation). Previous attempts to deliver aerosolized lung surfactants yielded discouraging results, largely due to inefficient delivery of the aerosol. Therefore, a patient interface was engineered to efficiently direct aerosolized KL4 lung surfactant to the lungs of neonates in conjunction with nCPAP. Two custom components were designed which linked the aerosol generator to the nasal prongs: 1) an aerosol Conditioning System (CS) to modulate the aerosol and control deposition, and 2) a Prong Adapter (PA) to integrate the CS with ventilator circuits and nasal prongs. These components were cGMP produced by injection molding. An Aeroneb Professional Nebulizer System (Aerogen Inc.) and cGMP produced KL4 lung surfactant at 20mg/ml total phospholipid were the aerosol generator and lung surfactant studied, respectively. The interface components were evaluated in vitro using an InfantStar ventilator. A Harvard Ventilator was used to simulate infant breathing. This novel interface was able to direct 17 +/-2 mg/min of lung surfactant (0.4 mg-total phospholipids per minute) aerosolized by the Aeroneb Pro to the infant-simulator. In contrast, only 8 mg/min was delivered to the simulated infant using an aerosol generator in-line with the CPAP circuit for the same operating conditions (p<0.005). Ventilator gas flow rates, temperature, and nasal prong size were all examined and not found to have a significant impact on the efficiency of aerosol delivery to the simulated infant. In short, this system holds promise to combine the life saving benefits of lung surfactant replacement with nCPAP therapies for infants with RDS and is currently undergoing clinical testing.