Background: No conclusive data exists supporting the use of any prokinetic agent in the postoperative setting. The study was designed to examine the effect of erythromycin on small bowel motility in a placebo-controlled trial of post gastric bypass patients utilizing a standardized nuclear medicine test. Methods: A consecutive series of 21 patients undergoing elective gastric bypass surgery for morbid obesity between September 1999 and March 2001 were enrolled in this prospective double-blind randomized controlled trial. Standard open, divided gastric bypass was performed. Patients were randomized to receive either erythromycin 250 mg I. V. (11 patients) or placebo (10 patients) every 8 hours. On postoperative day 2, a hepatic iminodiacetic acid (HIDA) scan was obtained. Tracer movement through the biliary tree and proximal small bowel was quantified and compared. Results:Tracer clearance from the liver and biliary tree was no different between groups from time of injection through 1 hour. Tracer material clearance from the duodenum into the jejunum was no different between the erythromycin and control groups at 1 hour, 37% ±13% and 37% ±22% respectively (P=0.95). At 4 hours, clearance was greater in the erythromycin group, 77%±6%, compared to control, 60%±20% (P =0.036). The rate of tracer change between hour 1 and 4 (slope) was steeper in the erythromycin group (P=0.048). Conclusions: Erythromycin increases intestinal transit in the postoperative setting.