Bubble continuous positive airway pressure (B-CPAP) applies small-amplitude, high-frequency oscillations in airway pressure (DeltaPaw) that may improve gas exchange in infants with respiratory disease. We developed a device, high-amplitude B-CPAP (HAB-CPAP), which provides greater DeltaPaw than B-CPAP provides. We studied the effects of different operational parameters on DeltaPaw and volumes of gas delivered to a mechanical infant lung model. In vivo studies tested the hypothesis that HAB-CPAP provides noninvasive respiratory support greater than that provided by B-CPAP. Lavaged juvenile rabbits were stabilized on ventilator nasal CPAP. The animals were then supported at the same mean airway pressure, bias flow, and fraction of inspired oxygen (FiO2) required for stabilization, whereas the bubbler angle was varied in a randomized crossover design at exit angles, relative to vertical, of 0 (HAB-CPAP0; equivalent to conventional B-CPAP), 90 (HAB-CPAP90), and 135 degrees (HAB-CPAP135). Arterial blood gases and pressure-rate product (PRP) were measured after 15 min at each bubbler angle. Pao2 levels were higher (p<0.007) with HAB-CPAP135 than with conventional B-CPAP. PaCO2 levels did not differ (p=0.073) among the three bubbler configurations. PRP with HAB-CPAP135 were half of the PRP with HAB-CPAP0 or HAB-CPAP90 (p=0.001). These results indicate that HAB-CPAP135 provides greater respiratory support than conventional B-CPAP does.