Background <p>Preoxygenation is crucial for airway management safety. The standard method for preoxygenation is tidal volume breathing (TVB). This study aimed to determine whether an algorithmic approach, which involves stepwise adding pressure support ventilation (PSV) and positive end-expiratory pressure (PEEP) when TVB is inadequate, would improve preoxygenation.</p> Methods <p>Two hundred patients planned for general anesthesia and having end-tidal oxygen (ETO₂) &lt; 90% after 3&#xa0;min TVB were randomly divided into two: TVB was continued or 6&#xa0;cmH₂O PSV was added. After 1&#xa0;min PSV (i.e., at minute 4), patients still with ETO₂ &lt; 90% were divided into two again: either PSV was continued or 4&#xa0;cmH₂O PEEP was also added to PSV. The primary outcome was the time required to achieve ETO₂ ≥ 90%. Adverse effects were noted.</p> Results <p>After 4&#xa0;min, patients with adequate preoxygenation were significantly higher with PSV (76%) compared with TVB (52%, <i>P</i> &lt; 0.001). After 5&#xa0;min, it was 97% and 100%, respectively. The mean durations of adequate preoxygenation with TVB, PSV, and PSV-PEEP between 4 and 5&#xa0;min were 274.90 ± 18.55, 268.94 ± 12.24, and 252.38 ± 7.46&#xa0;s, respectively. The differences between TVB and PSV-PEEP (<i>P</i> &lt; 0.001) and between PSV and PSV-PEEP (<i>P</i> = 0.001) were significant. Total time was significantly longer with TVB (237.17 ± 40.31&#xa0;s) compared with PSV (222.63 ± 27.24&#xa0;s; <i>P</i> = 0.003).</p> Conclusions <p>An algorithmic approach, stepwise adding PSV and PEEP in patients inadequately preoxygenated with standard TVB, may improve adequate preoxygenation in all patients and reduces the time required. This statistical difference was significant, and although its clinical relevance may differ based on patient condition, it may support safer airway management in critically ill or high-risk patients. No serious adverse effects were observed.</p> Trial registration <p>NCT06736197.</p>