PURPOSE: To determine the association between opioid use and the occurrence of postoperative paralytic ileus (POI) after different types of surgery. METHODS: The PHARMO database was used to perform a case control study in which intramural drug utilsation data were linked to hospital discharge diagnoses. All patients admitted for digestive, abdominal or genito-urinary surgeries were selected in 1998-2003. Cases with coded POI (ICD-9-CM 560.1 and 564.4) and controls with no POI were matched 1:10. The association between coded POI and opioid use was assessed using conditional logistic regression. RESULTS: In 0.2% of all admissions (total of 180,279), patients developed POI and in 18% of all admissions, patients received opioids. Three hundred and sixty-six cases with POI were selected with their matching controls. The use of (nico)morphine was associated with the risk for developing POI (odds ratio (OR) 12.1, 95% confidence interval (CI) 5.4-27.1). The association between opioids and POI was most obvious in patients with abdominal surgery (OR 33.8, 95%CI 6.2-184.6) and patients without colon/colorectal/rectal tumours (OR 13.2, 95%CI 5.7-30.3). CONCLUSION: This study demonstrated a distinct association between the use of opioids, in particular natural opium alkaloids, and the risk for coded POI. Copyright (c) 2006 John Wiley & Sons, Ltd.