Background: The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. Methods: In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m2 who were scheduled for open thoracic or video-assisted thoracoscopic surgery under general anaesthesia requiring one-lung ventilation with a double-lumen tube, with a planned operative time of more than 60 min, and an expected duration of one-lung ventilation longer than that of two-lung ventilation. Patients were randomly assigned (1:1), using permuted blocks of random size (4, 6, and 8) and stratified by study site, to receive one-lung ventilation with either a higher PEEP of 10 cm H2O and periodic lung recruitment manoeuvres (high PEEP group) or a lower PEEP of 5 cm H2O without routine recruitment manoeuvres (low PEEP group). All patients received protective tidal volumes of 5 mL/kg predicted body weight during one-lung ventilation and 7 mL/kg predicted body weight during two-lung ventilation. Postoperative assessors were masked to treatment allocation. The primary outcome was a composite of PPCs during the first 5 postoperative days, including aspiration pneumonia, moderate or severe respiratory failure, acute respiratory distress syndrome (ARDS), pulmonary infection, atelectasis, cardiopulmonary oedema, pleural effusion, non-operative pneumothorax, pulmonary infiltrates, prolonged air leak, purulent pleuritis, pulmonary embolism, and pulmonary haemorrhage. A modified intention-to-treat analysis was performed, with patients analysed according to their assigned treatment group, except in cases of withdrawal of informed consent, cancellation of surgery, and or loss to follow-up. This trial is registered with ClinicalTrials.gov (NCT02963025) and is completed. Findings: Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference –2·68 percentage points [95% CI –6·36 to 1·01]; p=0·155). Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41–21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982). The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. Interpretation: In patients with a BMI of less than 35 kg/m2 undergoing thoracic surgery, one-lung ventilation using higher PEEP with recruitment manoeuvres, compared with lower PEEP without recruitment manoeuvres, did not reduce PPCs. The choice for intraoperative lung expansion or permissive atelectasis should take the individual gas-exchange and haemodynamic conditions into account, which might vary during the intraoperative period. Funding: Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universität Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasília, Brazil); and the Association of Anaesthetists of GB and Ireland.