Background: Erythromycin enhances gastric emptying and has been suggested to facilitate nasoenteric feeding tube placement in adults. Our primary objective was to evaluate the effect of erythromycin on the transpyloric passage of feeding tubes in critically ill children, and second, to evaluate the effect of erythromycin on the distal migration of duodenal feeding tubes. Methods: Seventy-four children were randomly assigned to receive erythromycin lactobionate (10 mg/kg) IV or equal volume of saline placebo 60 minutes before passage of a flexible weighted tip feeding tube. Abdominal radiographs were obtained 4 hours later to assess tube placement. If the tube was proximal to the third part of the duodenum, two additional doses of erythromycin/placebo were administered 6 hours apart. Those receiving additional doses had repeat radiographs 14 to 18 hours after tube placement. Results: The number of postpyloric feeding tubes was similar in the erythromycin and placebo treated groups 4 hours after tube insertion (23/37 vs 27/37, p = .5). Of those with prepyloric tubes at 4 hours, none in the erythromycin group and 3 in the placebo group had the tube migrate to the postpyloric position by 14 to 18 hours (p < .05). Of those with postpyloric tubes proximal to the third part of the duodenum at 4 hours, additional doses of erythromycin did not cause more tubes to advance further into the intestine than did placebo (p = .6). Conclusions: Erythromycin does not facilitate transpyloric passage of feeding tubes in critically ill children. The distal migration of duodenal tubes further into the small bowel is also not enhanced by erythromycin.