Approximately 2.5 million newborns die annually and the vast majority of deaths occur in low- and middle-income countries. Although the most common etiologies behind neonatal death often present with respiratory distress, there is currently a critical lack of access to noninvasive respiratory support modalities in low-resource and austere settings. Designs for low-cost bubble continuous positive airway pressure (CPAP) devices have been published for use in resource-limited settings, however, there exists a need for a low-cost device that can provide bilevel positive pressure to sustain neonates requiring additional ventilatory support. The objective of this study was to evaluate the ability of a novel low-cost bubble bilevel positive airway pressure (BiPAP) device to deliver specific pressures both in vitro and in vivo in a piglet model. A Bubble BiPAP was fabricated using a modified nasal cannula, extension tubing, microcontroller, servo motor, battery pack, stick, and bucket of water totaling less than 50 US dollars. An in vitro model was constructed with a simulated nasopharynx having a defined nare size and nasopharyngeal volume. Intrapharyngeal pressures were measured every 0.1 second during operation of the device at pressures of 20/10 cmH2O. Performance of the Bubble BiPAP was compared to a standard cannula driven by a modern hospital ventilator in nasal intermittent positive pressure ventilation (NIPPV) mode. After ensuring the device could meet targets in vitro, a pilot study was performed in vivo in 2 anesthetized 8 kg piglets. Venous blood gases, oxygen saturations, and end-tidal capnography values were recorded every 5-10 minutes, and pressures at the nares were recorded continuously. The Bubble BiPAP outperformed NIPPV in vitro in reaching goal pressure values of 20/10 cmH2O and this difference was more profound as leak increased (properly fitting cannula mean pressures 15.1 vs 13.1 cmH2O, smaller fitting cannula 12.4 vs 7.5, smallest fitting cannula 5.6 vs 1.8; p< 0.001). During the in vivo evaluation, the Bubble BiPAP functioned reliably over 90 minutes without pause. The most effective Bubble BiPAP settings in vivo were 20/10 cmH20, RR 30, and iTime of 1 second; however, the piglet slowly became hypercarbic over a 45-minute period with ETCO2 increasing from 59-66 mmHg with a rate of rise (RoR) of 0.15 mmHg/minute. In contrast, on bubble CPAP, ETCO2 levels increased from 35-59 mmHg after 4 minutes with a RoR of 6 mmHg/minute indicating failure of therapy. ETCO2 values correlated well with blood gas pCO2 levels (Pearson r=0.97, p< 0.001). Results from this study demonstrated that the novel Bubble BiPAP consistently delivered bilevel pressures at the nares close to goal parameters and functioned reliably in a piglet model. Although the Bubble BiPAP ventilated a piglet in vivo, the inability to reduce CO2 levels may be due to the piglets having larger tidal volumes than the device was originally intended for and/or the piglets’ anesthetized state. Work is in progress to develop an advanced prototype and improve in vitro and in vivo testing models. A provisional patent application was filed with the US Patent and Trademark Office (No. 63/644,558).