BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.