Infectious agents, including parasites, often have oncogenic potential. However, there has been no study on the association between Strongyloides stercoralis infection and cancer risk. Therefore, we investigated the relationship between S. stercoralis infection and the occurrence of hepato-pancreato-biliary cancer. This case-control study examined 1,654 patients aged>or=50 years in the Department of Medicine and Therapeutics, Ryukyu University Hospital, Okinawa, Japan, between 1991 and 2005. There were 196 patients with hepato-pancreato-biliary cancer and 1,458 control patients without cancer. The association between S. stercoralis infection and cancer was analyzed by logistic regression analysis adjusted for human T cell lymphotropic virus type 1 infection, age, and sex. The prevalence of S. stercoralis infection in controls and biliary tract cancer was significantly different at 7.5 and 18.4%, respectively (P=0.03, adjusted odds ratio 2.7, 95% confidence intervals 1.1-6.3). In conclusion, our study indicates that the prevalence of S. stercoralis infection in patients with biliary tract cancer appears significantly higher than that in control patients. Thus, we propose that S. stercoralis infection is a risk factor for biliary tract cancer.