Background: Driving pressure (ΔP = plateau pressure − PEEP) has been proposed as a key ventilatory target linked to postoperative pulmonary complications (PPCs) and survival. Whether ΔP-guided strategies outperform conventional lung-protective ventilation across surgical and critical-care settings remains uncertain. Methods: Following PRISMA principles, we synthesized nine original studies provided by the author (randomized trials and physiologic studies) spanning open and minimally invasive surgery, thoracic one-lung ventilation, cardiac surgery, and ARDS. Primary outcomes were PPCs or ventilator-free days; secondary outcomes included oxygenation, compliance, atelectasis, and mechanical power. Results: Single-centre RCTs in open upper abdominal surgery and thoracic one-lung ventilation reported fewer PPCs with individualized PEEP targeting the lowest ΔP (38.8% vs 62.7% after open abdominal surgery; 5.5% vs 12.2% after thoracic surgery). Larger multicentre trials in thoracic surgery and patients at risk during laparoscopic/robotic procedures showed improved mechanics and less desaturation but no reduction in composite PPCs. In cardiac surgery and ARDS, ΔP-guided strategies decreased ΔP or mechanical power without improving major clinical outcomes. Overall, benefits were consistent for physiologic endpoints (oxygenation, compliance, atelectasis/mechanical power) but mixed for hard outcomes. Conclusions: ΔP guided ventilation improve intraoperative physiology and reduce specific complications in select settings, but multicentre evidence shows no consistent reduction in composite PPCs or ventilator-free days. Standardized protocols and adequately powered trials are needed across diverse populations.