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Patients with chronic hepatitis B infection (CHB) have an increased risk for death from liver cirrhosis and hepatocellular carcinoma (HCC). In the United States, only an estimated 37% of adults with chronic hepatitis B diagnosis without cirrhosis receive monitoring with at least an annual alanine transaminase (ALT) and hepatitis B deoxyribonucleic acid (DNA), and an estimated 59% receive antiviral treatment when they develop active hepatitis or cirrhosis. A Markov model was used to calculate the costs, health impact and cost-effectiveness of increased monitoring of adults with HBeAg negative inactive or HBeAg positive immune tolerant CHB who have no cirrhosis or significant fibrosis and are not recommended by the current American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines to receive antiviral treatment, and to assess whether the addition of HCC surveillance would be cost-effective. For every 100,000 adults with CHB who were initially not recommended for treatment, if the monitoring rate increased from the current 37% to 90% and treatment rate increased from 59% to 80%, 4,600 cases of cirrhosis, 2,450 cases of HCC and 4,700 HBV-related deaths would be averted with a gain of 45,000 QALYs and a savings of $180 million in lifetime health care costs. At a willingness to pay threshold of $100,000/QALY, the addition of HCC surveillance with the standard recommended biannual liver ultrasound and alfa fetoprotein levels is likely cost-effective if the HCC risk ≥ 0.55%/year. Regular monitoring of persons with inactive or immune tolerant CHB who are initially not recommended to receive antiviral treatment in the United States is cost-saving. The addition of HCC surveillance with biannual US and AFP would be cost-effective for individuals with HCC incidence ≥ 0.55%/year. [ABSTRACT FROM AUTHOR]