Introduction: The largest cohort of critically ill patients evaluating intragastric and small intestinal delivery of nutrients was recently reported. This systematic review included recent data to compare the effects of small bowel and intragastric delivery of enteral nutrients in adult critically ill patients. Methods: This is a systematic review of all randomised controlled studies published between 1990 and March 2013 that reported the effects of the route of enteral feeding in the critically ill on clinically important outcomes. Results: Data from 15 level-2 studies were included. Small bowel feeding was associated with a reduced risk of pneumonia (Relative Risk, RR, small intestinal vs. intragastric: 0.75 [95 confidence interval 0.60-0.93]; P = 0.01; I2=11 ). The point estimate was similar when only studies using microbiological data were included. Duration of ventilation (weighted mean difference: -0.36 days [-2.02-1.30]; P = 0.65; I2=42 ), length of ICU stay (WMD: 0.49 days, [-1.36-2.33]; P = 0.60; I2=81 ) and mortality (RR 1.01 [0.83-1.24]; p = 0.92; I2=0 ) were unaffected by the route of feeding. While data were limited, and there was substantial statistical heterogeneity, there was significantly improved nutrient intake via the small intestinal route ( goal rate received: 11 [5-16]; P = 0.0004; I2=88 ). Conclusions: Use of small intestinal feeding may improve nutritional intake and reduce the incidence of ICU-acquired pneumonia. In unselected critically ill patients other clinically important outcomes were unaffected by the site of feeding tube.