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More than 2.4 million people were estimated to have chronic hepatitis C (CHC) in the United States from 2017 to 2020. Direct-acting antiviral (DAA) therapy can cure hepatitis C and limit its complications, including liver cirrhosis and hepatocellular carcinoma (HCC). This study aims to estimate the lifetime medical cost burden of CHC in the United States. We estimated the lifetime direct medical costs of CHC by disease stage, using medical and laboratory claims data and a Markov transition model. The analysis considered the cost of CHC separately for persons treated with DAAs and untreated persons. We estimated the cost of health care utilization associated with CHC per person for the initial year, remaining life years, and overall lifetimes and used these costs to estimate lifetime costs for the 2020 cohort of adults with CHC in the United States in 2020. On average, medical costs per person in a disease stage were $89,070 (treated) and $150,669 (untreated) for non-cirrhosis, $104,961 (treated) and $197,469 (untreated) for cirrhosis, $59,120 (treated) and $208,646 (untreated) for decompensated cirrhosis, $44,876 (treated) and $113,975 (untreated) for hepatocellular carcinoma. The overall per person lifetime medical cost (weighted by the percentage of newly reported cases in each disease stage) was $90,089 (treated) and $155,930 (untreated). For a cohort of 2.228 million people, the projected total medical cost burden of CHC in 2022 dollars would be $200 billion if all were treated using DAAs, compared to $347 billion if all were untreated. We found a substantial reduction in the overall lifetime medical costs of hepatitis C for persons treated with DAAs compared to untreated persons. These potential health care savings from expanded hepatitis C treatment underscore the importance of expanding HCV testing and DAA treatment as core components of the national strategy for hepatitis C elimination.