Sphincterotomy of the ampulla of Vater--a common diagnostic and therapeutic procedure that is sometimes done during endoscopic retrograde cholangiography (ERC)--allows reflux of intestinal content into the biliary tree. The resulting inflammation may contribute to malignant transformation of the biliary epithelium and therefore increase the risk of cholangiocarcinoma. We used data from population-based Danish health-care registries to examine the incidence of cholangiocarcinoma after ERC for 10 690 ERC patients who underwent sphincterotomy between 1977 and 2003 and 10,690 ERC patients who did not undergo sphincterotomy. Patients with sphincterotomy were matched to patients without sphincterotomy by sex and age at, calendar year of, and indication for ERC. The cholangiocarcinoma incidence rate for sphincterotomy patients was 404 per 100,000 person-years during the first year after ERC and decreased progressively at later times after ERC (79, 42, and 27 per 100,000 person-years during years 2, 3-5, and > 5, respectively). The corresponding rates for patients without sphincterotomy were 458, 12, 10, and 19 per 100,000 person-years, respectively. The gradual decrease in cholangiocarcinoma rate over time after ERC for sphincterotomy patients indicates that some of these patients had a cholangiocarcinoma that was present at the time of ERC but not diagnosed until 2-5 years later. The similar rates at the latest times after ERC suggest the lack of a causal association between sphincterotomy and cholangiocarcinoma.