Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP).Is obesity associated with increased incidence of VAP?Post-hoc analysis of the NUTRIREA-2 open-label RCT, performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock, and parenteral nutrition or enteral nutrition were included. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiological, and microbiological data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed using Fine and Gray model, with extubation, and death as competing risks.699 (30%) of the 2325 included patients had obesity. 224 first VAP episodes were diagnosed (60, and 164 in obese, and non-obese groups; respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (HR: 0.85, (95% CI 0.63-1.14), p=0.26). After adjustment on gender, McCabe score, age, anti-ulcer treatment, and SOFA at randomization, the incidence of VAP remained non-significant between obese and non-obese patients (HR 0.893 (95% CI 0.66-1.2), p=0.46). Although no significant difference was found in duration of mechanical ventilation, and ICU length of stay; 90-day mortality was significantly lower in obese than in non-obese patients (272 of 692 (39.3%) patients vs 718 of 1605 (44.7%), p=0.02). In a sub-group of patients (n=123) with available pepsin, and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and non-obese patients.Our results suggest that obesity has no significant impact on the incidence of VAP.