OBJECTIVE To provide proof-of-concept for a protocol applying a strategy of personalized mechanical ventilation in children with acute respiratory distress syndrome. Positive end-expiratory pressure and inspiratory pressure settings were optimized using real-time electrical impedance tomography aiming to maximize lung recruitment while minimizing lung overdistension. METHODS Prospective interventional trial. METHODS Two PICUs. METHODS Eight children with early acute respiratory distress syndrome (< 72 hr). METHODS On 3 consecutive days, electrical impedance tomography-guided positive end-expiratory pressure titration was performed by using regional compliance analysis. The Acute Respiratory Distress Network high/low positive end-expiratory pressure tables were used as patient's safety guardrails. Driving pressure was maintained constant. Algorithm includes the following: 1) recruitment of atelectasis: increasing positive end-expiratory pressure in steps of 4 mbar; 2) reduction of overdistension: decreasing positive end-expiratory pressure in steps of 2 mbar until electrical impedance tomography shows collapse; and 3) maintaining current positive end-expiratory pressure and check regional compliance every hour. In case of derecruitment start at step 1. RESULTS Lung areas classified by electrical impedance tomography as collapsed or overdistended were changed on average by -9.1% (95% CI, -13.7 to -4.4; p < 0.001) during titration. Collapse was changed by -9.9% (95% CI, -15.3 to -4.5; p < 0.001), while overdistension did not increase significantly (0.8%; 95% CI, -2.9 to 4.5; p = 0.650). A mean increase of the positive end-expiratory pressure level (1.4 mbar; 95% CI, 0.6-2.2; p = 0.008) occurred after titration. Global respiratory system compliance and gas exchange improved (global respiratory system compliance: 1.3 mL/mbar, 95% CI [-0.3 to 3.0], p = 0.026; Pao2: 17.6 mm Hg, 95% CI [7.8-27.5], p = 0.0039; and Pao2/Fio2 ratio: 55.2 mm Hg, 95% CI [27.3-83.2], p < 0.001, all values are change in pre vs post). CONCLUSIONS Electrical impedance tomography-guided positive end-expiratory pressure titration reduced regional lung collapse without significant increase of overdistension, while improving global compliance and gas exchange in children with acute respiratory distress syndrome.