Background: The gastrointestinal peptide hormones ghrelin and PYY have been shown to play a role in the regulation of metabolism and appetite. We investigate the effect of Biliopancreatic diversion with Roux-en-Y gastric bypass (BPD-RYGBP) on the circulating levels of ghrelin and peptide YY during the first 3 months postoperatively as compared to the effects of colectomy, an abdominal operation of similar severity. Methods: Fasting plasma levels of ghrelin and PYY were determined in 20 super-obese patients (BMI≥50) who underwent BPD-RYGBP and in 13 patients who underwent colectomy for large bowel cancer. Fasting plasma ghrelin and PYY levels were measured preoperatively and during the postoperative period on days 1, 3, 7, 30 and 90 in all patients of both groups, and at 1 year for 10 of the patients who had attained 1-year follow up. Results: Preoperatively, both plasma ghrelin and PYY levels were lower in the BPD-RYGBP group of patients. A temporary decrease in plasma ghrelin levels was observed in both groups of patients during the immediate postoperative period, with a gradual return to preoperative levels by the 3rd month. In addition, ghrelin concentrations increased at 1 year to levels 40% higher than those at baseline, in 10 of the BPD-RYGBP patients who had completed the 1-year follow-up (P=0.004). Plasma PYY levels in the colectomy group decreased in the first 3 postoperative days and then returned to baseline. In contrast, PYY levels in the BPD-RYGBP group did not change during the early postoperative period but increased to levels 50% higher at 3 months (P<0.001) and 170% higher at 1 year (P<0.001) than the baseline. Conclusions: The great postoperative increase in the levels of the anorexigenic peptide PYY following BPD-RYGBP may contribute to the reduced appetite observed after this type of bariatric surgery. The changes in ghrelin levels postoperatively make its contribution to the appetite suppression less likely.