Objective: To characterize pulmonary hemodynamic changes in relation to lung injury at 2 time points [48 h (H48) and 168 h (H168)] after pneumonectomy under intraoperative protective ventilation in order to improve postpneumonectomy pulmonary edema (PPE) prevention. Method: Fifteen pigs (25 ± 1.9 kg) were randomly allocated to nonsurgical (control, n = 5) and surgical (H48 and H168) groups. A left pneumonectomy under volume-controlled one-lung ventilation (OLV) (low tidal volume, positive end-expiratory pressure = 4 cm H2O, inspired oxygen fraction = 50%) was performed in surgical animals. Mean pulmonary artery pressure (MPAP) and pulmonary artery occlusion pressure were recorded. Pulmonary vascular resistance (PVR) was calculated. Pulmonary damage score (PDS) and bronchoalveolar albumin level were evaluated. Data were collected after induction (T0), after OLV (T1), after left pneumonectomy (T2), and at H48 or H168 (T3). Results: Pneumonectomy caused precapillary pulmonary arterial hypertension (PAH) measured at T3 H48 (36.2 ± 3.67 mm Hg). PAH was delayed temporarily (both after OLV and after pneumonectomy) (p < 0.001), and linked with PVR (r = 0.93; p < 0.05). PDS and bronchoalveolar albumin level varied with MPAP (r = 0.76; p < 0.001 and r = 0.55; p < 0.05). Conclusion: Given that PAH is delayed and related to PVR increase, indicating secondary pulmonary vascular bed adaptation limits, pharmacological treatment should focus on a delayed failure in pulmonary capacitance in patients at risk of PPE.