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To evaluate the prevalence and risk factors of Clonorchis sinensis infection, an epidemiologic survey was performed (3,169 residents; age range: 30–87 years; mean age = 59; 1,973 women) in three areas with different mortality rates of cholangiocarcinoma. C. sinensis prevalence was 2.1% in Chuncheon, 7.8% in Chungju, and 31.3% in Haman, where cholangiocarcinoma incidence rate was 0.3, 1.8, and 5.5 per 100,000 persons, respectively. Of the four major risk factors for C. sinensis (male sex, alcohol consumption, raw freshwater fish intake, and area of residence), area was the strongest. Efforts to discourage raw freshwater fish intake, treat egg carriers, and protect water sources from C. sinensis contamination should be strengthened in the Republic of Korea.