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Objective: The risk-benefit profile of trans-pyloric versus gastric feeding in mechanically ventilated patients has not been definitively established.Our objective was to evaluate the risks and benefits of trans-pyloric feeding compared with gastric feeding in mechanically ventilated patients.Data Sources: We systematically searched Medline, Google Scholar, EMBASE, and the Cochrane Central Register of Controlled Trials databases for eligible articles through June 21, 2013.Study Selection: Randomized controlled trials that reported a comparison between gastric and trans-pyloric feeding in MV patients.Data Extraction: Two reviewers independently extracted data on populations, methods, outcomes, and risk of bias.Ventilator-associated pneumonia was considered as the primary outcome.Data Synthesis: A total of 7 RCTs including 734 mechanically ventilated patients were identified and analyzed.Our pooled findings indicated that there was a significant reduction in VAP through trans-pyloric feeding comparing to gastric feeding (RR 1.58, 95%CI: 1.20 to 2.06 P=0.0009), but not in mortality(RR 0.87, 95% CI: 0.67 to 1.12 P=0.28), length of MV(MD 0.16, 95%CI:-0.43 to 0.75, P=0.59), length of stay in ICU(MD0.6, 95%CI:-1.37 to 2.58, P=0.55), incidence of diarrhea (RR 1.18, 95% CI: 0.82 to 1.70, P=0.36), incidence of abdominal distention (RR 1.26, 95% CI: 0.70 to 2.28, P=0.44).Conclusions: Trans-pyloric feeding in MV adults was associated with a significantly less incidence of VAP as compared to gastric feeding.There is insufficient evidence to support other benefits.