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Background  This trial aimed to evaluate the effects of a protective ventilation strategy on oxygenation/pulmonary indexes in patients undergoing robot-assisted radical prostatectomy (RARP) in the steep Trendelenburg position.    Methods  In phase 1, the most optimal positive end-expiratory pressure (PEEP) was determined in 25 patients at 11 cmH 2 O. In phase 2, 64 patients were randomized to the traditional ventilation group with tidal volume (VT) of 9 ml/kg of predicted body weight (PBW) and the protective ventilation group with VT of 7 ml/kg of PBW with optimal PEEP and recruitment maneuvers (RMs). The primary endpoint was the intraoperative and postoperative PaO 2 /FiO 2 . The secondary endpoints were the PaCO 2 , SpO 2 , modified clinical pulmonary infection score (mCPIS), and the rate of complications in the postoperative period.    Results  Compared with controls, PaO 2 /FiO 2  in the protective group increased after the second RM ( P =0.018), and the difference remained until postoperative day 3 ( P =0.043). PaCO 2  showed transient accumulation in the protective group after the first RM (T2), but this phenomenon disappeared with time. SpO 2  in the protective group was significantly higher during the first three postoperative days. Lung compliance was significantly improved after the second RM in the protective group ( P =0.025). The mCPIS was lower in the protective group on postoperative day 3 (0.59 (1.09) vs. 1.46 (1.27),  P =0.010).    Conclusion  A protective ventilation strategy with lower VT combined with optimal PEEP and RMs could improve oxygenation and reduce mCPIS in patients undergoing RARP.    Trial registration  ChiCTR  ChiCTR1800015626 . Registered on 12 April 2018.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13063-021-05310-9.

Protective mechanical ventilation with optimal PEEP during RARP improves oxygenation and pulmonary indexes