Heliox (Hx) gas has been shown to improve pulmonary function in infants, but methods for its delivery are invasive and problematic. To this end, we modified an Isolette (Hill-Rom Air-Shields) infant incubator (Hxl) to deliver Hx respiratory gas mixtures noninvasively while providing thermal stability for neonatal care in the Neonatal Intensive Care Unit (NICU). In vitro tests and in vivo animal studies were performed to compare the original design specifications and established baseline performance criteria for the Hxl design. The experimental environments at 50% and 80% relative humidity (RH) consisted of helium (He) with 21% and 50% O2 and control (C) of 21% and 50% O2 with the balance nitrogen (N). Elapsed times to steady state (SS) and recovery time back to SS (OCDss) due to opening and closing the door were recorded for each variable. All rabbits survived and appeared comfortable during all experimental conditions. These data show that the newly designed Isolette provides similar thermal, O2, CO2, and RH responses as the control incubator. Based on these positive safety/efficacy studies, study of the therapeutic impact of Hxl care on neonatal growth and development is in progress.