Postoperative pulmonary complications (PPC) affect over 10% of surgical patients, especially after abdominal, thoracic, or cardiac surgery. Understanding PPC’s pathophysiology and risk factors provides an effective framework for prevention strategies. Significant alterations of the respiratory function occur in all patients undergoing major surgery, especially if the surgical site is close to the diaphragm. The main changes observed are a reduction in lung volumes, with the development of restrictive patterns of respiratory mechanics, atelectasis, and diaphragmatic dysfunction. Hypoxemia often develops in patients after major surgery and may lead to acute respiratory failure (ARF). Postoperative ARF may require reintubation, which has been associated with mortality and healthcare-associated pneumonia. The Peri-Operative Positive Pressure (P.O.P) Ventilation concept includes multiple interventions ranging from positive pressure pre-oxygenation to intraoperative lung protective ventilation and tailored postoperative noninvasive respiratory support. Such strategies aim to mitigate the onset of ARF and prevent a reduction in lung volumes. Despite the inevitability of respiratory function alterations after surgery and anesthesia, perioperative interventions can significantly reduce complications. Positive pressure pre-oxygenation enhances the safety of the intubation procedure and prevents the decrease in lung volumes. Intraoperative lung-protective ventilation associating low to moderate tidal volumes based on predicted body weight, positive end-expiratory pressure, and careful recruitment maneuvers have been effective in decreasing PPC. The respective roles of noninvasive ventilation (NIV) and high-flow nasal oxygenation (HFNO) in preventing PPC remain to be clarified. Their efficacy in preventing the onset of ARF may depend on the ability to identify high-risk patients and tailor interventions accordingly. Current evidence supports curative NIV as the gold standard to treat postoperative ARF in comparison to conventional oxygen therapy or HFNO. As the understanding of the complex interplay between major surgery and respiratory function evolves, so must approaches to tailoring perioperative ventilation support.