Background: Strategies for managing respiratory motion, specifically motion-encompassing methods, in radiation therapy typically assume reproducible breathing. In reality, respiratory motion variations occur and ultimately cause tumor motion variations, which can result in differences between the planned and delivered dose distributions. Therefore, breathing guidance techniques have been investigated to improve respiratory reproducibility. To our knowledge, bilevel positive airway pressure (BIPAP) ventilation assistance has not been previously investigated as a technique for improving respiratory reproducibility and is the focus of this work. Methods and Materials: Ten patients undergoing radiation therapy treatment for cancers affected by respiratory motion (eg, lung and esophagus) participated in sessions in which their breathing was recorded during their course of treatment; these sessions occurred either before or after radiation treatments. Both unassisted free-breathing (FB) and BIPAP ventilation-assisted respiratory volume data were collected from each patient using spirometry. Patients used 2 different BIPAP ventilators (fixed BIPAP and flexible BIPAP), each configured to deliver the same volume of air per breath (ie, tidal volume). The flexible BIPAP ventilator permitted patient triggering (ie, it permitted patients to initiate each breath), and the fixed BIPAP did not. Intrasession and intersession metrics quantifying tidal volume variations were calculated and compared between the specific breathing platforms (FB or BIPAP). In addition, patient tolerance of both BIPAP ventilators was qualitatively assessed through verbal feedback. Results: Both BIPAP ventilators were tolerated by patients, although the fixed BIPAP was not as well tolerated as the flexible BIPAP. Both BIPAP ventilators showed significant reductions (P <.05) in intrasession tidal volume variation compared with FB. However, only the fixed BIPAP significantly reduced the intersession tidal volume variation compared with FB. Conclusions: Based on the established correlation between tidal volume and tumor motion, any reduction of the tidal volume variation could result in reduced tumor motion variation. Fixed BIPAP ventilation was found to be tolerated by patients and was shown to significantly reduce intrasession and intersession tidal volume variations compared with FB. Therefore, future investigation into the potential of fixed BIPAP ventilation is warranted to define the possible clinical benefits.