Objective <p>The study aimed to investigate the role of electrical impedance tomography (EIT)-guided individualized positive end-expiratory pressure (PEEP) in surgical patients under lateral position.</p> Methods <p>The urological patients undergoing elective laparoscopic surgery were randomly allocated to either the PEEP_EIT (titrated with EIT) or PEEP₅ (fixed PEEP = 5cmH₂O) groups. The PEEP titration protocol commenced at 3 cmH₂O, with increments of 2 cmH₂O every 2&#xa0;min until reaching 17 cmH₂O. Once the EIT-titrated optimal PEEP level was determined with minimized regional overdistension and collapse, it was maintained until the end of surgery. The PaO₂/FiO₂ ratio, respiratory mechanics parameters and hemodynamic parameters were recorded at 5&#xa0;min before anesthesia induction (T₀), 5&#xa0;min after PEEP setting (T₁), at the end of surgery (T₂), and 30&#xa0;min after extubation (T₃).</p> Results <p>A total of 46 subjects were randomized. The median PEEP was 13 cmH₂O [25th − 75th percentiles, 11–14 cmH₂O] in the PEEP_EIT group. The PEEP_EIT group had higher PaO₂/FiO₂ ratio (423.2 ± 42.2 vs. 349.7 ± 48.0, <i>P</i>&lt;0.001) before extubation compared with the PEEP₅ group. Further, PEEP_EIT group had higher plateau pressure and dynamic compliance, while lower driving pressure at both T₁ (all <i>P</i> &lt; 0.05) and T₂ (<i>P</i> &lt; 0.05) time points. Hemodynamic changes were similar in two groups (<i>P</i> &gt; 0.05). There was no significant statistical difference in PaO₂/FiO₂ ratio at 30&#xa0;min after extubation between the two groups (379.7 ± 38.2 vs. 381.6 ± 54.0, <i>P</i> = 0.896).</p> Conclusion <p>Employing an EIT-guided individualized PEEP level during the surgery under lateral position may improve the pulmonary ventilation and respiratory mechanics, potentially improving oxygenation. However, this improved oxygenation seems not to be maintained after extubation.</p> Trial registration <p>China Clinical Trial Registration Center Identifier ChiCTR2100053895. Registered 02/12/2021.</p>