ObjectiveTo evaluate the efficacy of intravenous erythromycin as a method to facilitate feeding tube placement into the small intestine in critically ill patients.DesignDouble blind, randomized, controlled trial.SettingMedical and surgical intensive care units in an academic medical center.PatientsProspective cohort of 36 consecutive adults requiring intensive care unit care and enteral tube feeding for nutritional support.InterventionInfusion of a single dose of intravenous erythromycin (500 mg) or saline before placement of 10-Fr feeding tubes using a standardized active bedside protocol.Measurements and Main ResultsWe determined the success rate of feeding tube placement into or beyond the second portion of the duodenum and the time required for this procedure by experienced nurses. The feeding tube was considered to be postpyloric when the tip was in the second portion of the duodenum or beyond. The predictive value of a serial step-up in gastrointestinal aspirate pH from ≤5.0 to ≥6.0 was also determined. Use of intravenous erythromycin significantly improved the rate of feeding tube placement into the duodenum or jejunum (erythromycin group, 13 of 14 patients or 93% vs. the control group, 12 of 22 patients or 55%;p< .03). Erythromycin administration also significantly decreased the procedure time from 25 ± 3 to 15 ± 2 mins (p< .04). Feeding tube placement into either duodenum or jejunum was confirmed in all 18 patients with a pH step-up from ≤5.0 to ≥6.0.ConclusionA single bolus dose of intravenous erythromycin facilitates active bedside placement of postpyloric feeding tubes in critically ill adult patients.