BACKGROUND Pulmonary edema may alter alveolar bacterial clearance and infectivity. Manipulation of fluid balance aimed at reducing fluid overload may, therefore, influence ventilator-associated pneumonia (VAP) occurrence in intubated patients. The objective of the present study was to assess the impact of a depletive fluid-management strategy on ventilator-associated complication (VAC) and VAP occurrence during weaning from mechanical ventilation. METHODS We used data from the B-type Natriuretic Peptide for the Fluid Management of Weaning (BMW) randomized controlled trial performed in nine ICUs across Europe and America. We compared the cumulative incidence of VAC and VAP between the biomarker-driven, depletive fluid-management group and the usual-care group during the 14 days following randomization, using specific competing-risk methods (the Fine and Gray model). RESULTS Among the 304 patients analyzed, 41 experienced VAP, including 27 (17.8%) in the usual-care group vs 14 (9.2%) in the interventional group ( P = .03). From the Fine and Gray model, the probabilities of VAC and VAP occurrence were both significantly reduced with the interventional strategy while adjusting for weaning outcome as a competing event (subhazard ratios 25th-75th percentiles, 0.44 0.22-0.87, P = .02 and 0.50 0.25-0.96, P = .03, respectively). CONCLUSIONS Using proper competing risk analyses, we found that a depletive fluid-management strategy, when initiating the weaning process, has the potential for lowering VAP risk in patients who are mechanically ventilated. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov