Background: Enteral feeding provides nutrients for patients who require endotracheal tubes and mechanical ventilation. There is a presumed increase in the risk of ventilator-associated pneumonia (VAP) with tube feeding. This has stimulated the development of procedures for duodenal intubation and small intestinal (SI) feeding as primary prophylaxes to prevent VAP, Objective: To investigate the rate of VAP and adequacy of nutrient delivery with gastric (G) vs. SI feeding. Design: A prospective, randomized, controlled trial. Setting: A medical intensive care unit of a county hospital. Patients: A total of 44 endotracheally intubated, mechanically ventilated patients requiring enteral nutrition, Intervention: Subjects were randomized to receive enteral nutrition via G or SI feeding. Protocols directed the placement of the feeding tube and the infusion of enteral nutrition and defined the radiographic and clinical criteria for a diagnosis of VAP. Measurements and Outcomes: The incidence of VAP and the adequacy of nutritional supplementation were prospectively followed. The relative risk of VAP with SI was 1.1 (95% confidence interval 0.96-2.44) compared with G, The SI group received a greater percentage of their caloric requirements (SI 69 +/- 7% vs. G 47 +/- 7%, mean +/- SEM, p < .05), Mortality did not differ between G (26 +/- 9%) and SI (24 +/- 10, p = .86). Conclusions: There is no clear difference in the incidence of VAP in SI compared with G enteral nutrition. Patients given feeding into the SI do receive higher calorie and protein intakes.