INTRODUCTION: To compare outcomes from early post-pyloric to gastric feeding in ventilated, critically ill patients in a medical intensive care unit (ICU). METHODS: Prospective randomized study. Ventilated patients were randomly assigned to receive enteral feed via a nasogastric or a post-pyloric tube. Post-pyloric tubes were inserted by the bedside nurse and placement was confirmed radiographically. RESULTS: A total of 104 patients were enrolled, 54 in the gastric group and 50 in the post-pyloric group. Bedside post-pyloric tube insertion was successful in 80% of patients. Patients who failed post-pyloric insertion were fed via the nasogastric route, but were analysed on an intent-to treat basis. A per protocol analysis was also performed. Baseline characteristics were similar for all except Acute Physiology and Chronic Health Evaluation II (APACHE II) score, which was higher in the post-pyloric group. There was no difference in length of stay or ventilator days. The gastric group was quicker to initiate feed 4.3 hours (2.9 - 6.5 hours) as compared to post-pyloric group 6.6 hours (4.5 - 13.0 hours) (P = 0.0002). The time to reach target feeds from admission was also faster in gastric group: 8.7 hours (7.6 - 13.0 hours) compared to 12.3 hours (8.9 - 17.5 hours). The average daily energy and protein deficit were lower in gastric group 73 Kcal (2 - 288 Kcal) and 3.5 g (0 - 15 g) compared to 167 Kcal (70 - 411 Kcal) and 6.5 g (2.8 - 17.3 g) respectively but was only statistically significant for the average energy deficit (P = 0.035). This difference disappeared in the per protocol analysis. Complication rates were similar. CONCLUSIONS: Early post-pyloric feeding offers no advantage over early gastric feeding in terms of overall nutrition received and complications TRIAL REGISTRATION: Clinical Trial: anzctr.org.au:ACTRN12606000367549.