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Objective To explore the effect of protective ventilation strategies based on individualized positive end expiratory pressure (PEEP) regulated by driving pressure (Pd) in infants under OLV. Methods Sixty infants undergoing elective thoracoscopic surgery were randomly divided into the control group and driving pressure group, with 30 cases in each group. The two groups were compared in terms of MAP, HR, tidal volume (Vt), PEEP, Pd, airway peak pressure (Pk), and static lung compliance (Cs), and arterial blood gas during OLV before the artificial pneumothorax (T0), 10 min (T,), 30 min (T2), and 60 min (T3) after the artificial pneumothorax, and right at the end of the artificial pneumothorax (T4). Results There were no significant differences in MAP, HR, and Vt between the two groups at all the time points (P > 0.05). Both groups showed the increase in Pd and Pk and decresase in Cs at T,, T2, and T3 (all P < 0.05). PaO2 and OI in both group were decreased and PaCO2 was increased at T2 (all P < 0.05). Compared with the control group, the driving pressure group presented lower Pd and Pk, higher PEEP and Cs at T,, T2, and T3 (P < 0.05), and higher PaO2 and OI (P < 0.05) and no significant differences in PaCO2 and FiO2 at T2 (P < 0.05). The rate of rescue ventilation during OLV was lower in the driving pressure group (2 cases) than in the control group (9 cases) (6.9% versus 32.4%, P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P < 0.05). Conclusion The individualized positive end expiratory pressure (PEEP) regulated by Pd can optimize the PEEP settings upon infant individuals under OLV and improve the compliance and oxygenation of ventilated lung. [ABSTRACT FROM AUTHOR]