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We evaluated the effect of antibiotics administered via the respiratory tract to prevent the ventilator-associated pneumonia (VAP) in mechanically ventilated (MV) patients.We searched relevant articles for trials that evaluated the impact of prophylactic antibiotics administered through the respiratory tract on the occurrence of VAP. The end-point was the occurrence of VAP in MV patients.We included 6 comparative trials involving 1158 patients (632 received prophylactic antibiotic). Our meta-analysis revealed that prophylactic antibiotics administered through the respiratory tract reduced the occurrence of VAP when compared to placebo or no treatment (OR 0.53; 95% CI 0.34–0.84). This effect was seen when the antibiotics were given by nebulization (OR 0.46; 95% CI 0.22–0.97), but not when they were administered by intratracheal instillation (OR 0.57; 95% CI 0.28–1.15). We did not find a significant difference between the compared groups in the intensive care unit (ICU) mortality (OR 0.89; 95% CI 0.64–1.25). Antibiotic prophylaxis did not impact occurrence of VAP due to multidrug resistant (MDR) pathogens (OR 0.67; 95% CI 0.17–2.62).Prophylactic antibiotics administered through the respiratory tract by nebulization reduce the occurrence of VAP, without a significant effect on either the ICU mortality or occurrence of VAP due to MDR pathogens.Prophylactic antibiotics administered via the respiratory tract reduce the occurrence of ventilator-associated pneumonia.This prophylactic strategy didn't have significant effect on ICU mortality.