Background: Hepatolithiasis frequently results in severe complications. We conducted a cohort study to identify prognostic factors and to establish a hepatolithiasis severity classification system. Methods: The study cohort comprised 396 patients who were identified through a 1998 nationwide survey and followed up for 18 years or until death. Cox regression analysis was used to identify prognostic factors. Results: Median survival time of the patients was 308 (range 0–462) months. Of the 396 patients enrolled in the study, 118 (29.8%) died, most frequently from intrahepatic cholangiocarcinoma (25 patients, 21.2%). Age of ≥ 65 years at the time of initial diagnosis [hazard ratio (HR) 3.410], jaundice for ≥ 1 week during follow-up (HR 2.442), intrahepatic cholangiocarcinoma (HR 3.674), and liver cirrhosis (HR 5.061) were shown to be significant risk factors for death from any therapeutic course. The data led to a 3-grade disease severity classification system that incorporates intrahepatic cholangiocarcinoma and liver cirrhosis as major factors and age of ≥ 65 years and jaundice for ≥ 1 week during follow-up as minor factors. Survival rates differed significantly between grades. Conclusions: The proposed hepatolithiasis severity classification system can be used to assess prognosis and thereby improve patient outcomes.