Human physiology changes are often amplified in disease states and may be altered when a patient is mechanically ventilated. Normally, systolic blood pressure is slightly lower during inspiration than expiration due to the change in intrathoracic pressure. Pulsus paradoxus is a phenomenon in which the difference in systolic blood pressure (BP) between inspiration and expiration is more than 10 mmHg. When a patient is mechanically ventilated, the pattern of changes observed in pulsus paradoxus is reversed; that is, the systolic BP is higher during inspiration than expiration. In this article, the airway pressure and respiratory impedance tracings are used to demonstrate the inspiratory and expiratory phase of the respiratory cycle. Then BP can be determined with each respiratory phase. The difference in presentation of pulsus paradoxus in patients who are breathing spontaneously and with mechanical ventilation is described. A case study is also included to illustrate the presentation and treatment of pulsus paradoxus in a mechanically ventilated patient.