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Negative-pressure ventilation (NPV) is a form of noninvasive ventilation that has been recently utilized in pediatric acute respiratory failure. Negative-pressure ventilators apply negative pressure onto the chest wall via a cuirass to recruit areas of atelectasis. Continuous negative extrathoracic pressure, the most common mode, is similar to CPAP, where negative pressure is maintained at a constant level throughout the respiratory cycle while patients initiate their own breaths and continue to breathe spontaneously throughout. Control mode, which is similar to bi-level positive airway pressure, alternates negative pressure with positive pressure and controls both phases of breathing at a mandatory frequency set higher than the patient's spontaneous frequency. Supplemental oxygen is provided through a nasal cannula or face mask due of the lack of NPV devices' interface with the mouth or nose. NPV can improve preload to the heart and cardiac output (CO) in patients with restrictive right-ventricular physiology requiring CO augmentation and those with Fontan physiology. The purpose of this article is to review the physiological principles of spontaneous and NPV, examine the evidence supporting the use of NPV, give practical and meaningful guidance on its clinical application in the pediatric ICU, and summarize areas for future studies on its uses., Competing Interests: Mr Miller is a section editor for Respiratory Care. Mr Miller discloses a relationship with Saxe Communications. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)