OBJECTIVE: Chronic HBV is a serious infection for which few therapeutic options exist. The CDC estimates that 1.25 million Americans are chronically infected. We estimated the burden of disease in the United States from chronic HBV and its complications such as cirrhosis and hepatocellular carcinoma (HCC) using a disease simulation model. METHODS: We analyzed US data from the NHANES III survey to derive HBsAg prevalence estimates for the age groups 20-29, 30-39, 40-49, 50-59, 60+. Using US census data from 1991, we estimated the number of HBsAg carriers in the US in each age group. A Markov model with eight health states (seroconversion; chronic HBV; compensated cirrhosis; decompensated cirrhosis; HCC; transplant year 1; transplant year 2; death) was used to estimate disease burden from 2002 - 2012. Model simulation started from 1991; all subjects were started from the chronic HBV state; cycle length was one year; subjects could move between health states annually. Transition probabilities were derived from literature. Costs were derived from a claims database analysis (Pharmetrics) and literature. RESULTS: We estimated that 653,101 people had chronic HBV infection in 1991. These formed the base population for our analysis. We estimated that from 2002 - 2012, there will be 133,661 cirrhosis cases; 41,101 HCC cases; 6653 liver transplants; 133,722 deaths attributable to chronic HBV infection. The total direct medical costs for these cases was estimated at $9.4B over the same time frame. CONCLUSIONS: The results of this analysis shows that HBV infection is a significant burden on the US healthcare system. These results are probably an underestimation of the true burden given that our estimated patient population was half of the CDC estimate and incident cases are not accounted for. The availability of an effective antiviral agent capable of modifying the disease progression would decrease this economic burden to society.