AbstractPurpose: The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventila‑tor-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence ofVAP in comparison with the semirecumbent position (SRP).Methods: This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two pre‑planned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primaryoutcome, assessed by intention-to-treat analysis, was incidence of microbiologically confrmed VAP. Major secondaryoutcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay.Results: At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of beneft insecondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRPgroup were included in the fnal intention-to-treat analysis. The incidence of microbiologically confrmed VAP was0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02–1.03, p = 0.04). The28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95%CI 0.86–1.60, p = 0.32). Likewise, no diferences were found in other secondary outcomes. Six serious adverse eventswere described in LTP patients (p = 0.01 vs. SRP).