Positional changes are thought to affect hemodynamics, respiratory mechanics, and gas exchange after pneumonectomy. The objective of this study was to compare hemodynamic and respiratory parameters and gas exchange in different positions before and after pneumonectomy. Twenty pigs were anesthetized and mechanically ventilated. Seven received right-side pneumonectomy, seven received left-side pneumonectomy, and six were anesthetized but did not receive surgery and served as controls. Hemodynamic and respiratory parameters and blood gas values were measured in different positions (supine and right and left lateral decubitus). Minute mechanical ventilation was controlled throughout. Pneumonectomy resulted in significant reductions in MAP, accompanied by significant decreases in cardiac index, stroke volume index, global ejection fraction, and global end-diastolic volume index. Mean pulmonary arterial pressure and pulmonary vascular resistance index increased. PaCO2, airway resistance, and peak airway pressure increased, whereas PaO2 and lung compliance decreased. Hemodynamic and respiratory parameters and gas exchange were also significantly affected by changes in position with pneumonectomy. Mean arterial pressure, cardiac index, stroke volume index, global ejection fraction, and global end-diastolic volume index were significantly lower in the supine than in the right or left lateral decubitus position. PaO2 was significantly higher in a lateral position, with the remaining lung uppermost. Our findings suggest that avoiding the supine positioning after pneumonectomy may facilitate improvements in hemodynamics and a decreased risk of hypoxemia. The optimal position for gas exchange after pneumonectomy is a lateral position, with the remaining lung in the uppermost position.