OBJECTIVES: To quantify the financial burden of chronic hepatitis B (CHB) infection and its complications in a cost-of-illness study in Vietnam, a highly endemic country of hepatitis B virus (HBV) infection METHODS: The study adopted the micro-costing approach. For direct medical cost estimation, data were retrieved retrospectively from medical histories of inpatients and outpatients with various CHB infection stages in 2008 from a large referral hospital in Vietnam. For direct non-medical and indirect cost estimation, data were obtained from outpatients from the same hospital through face-to-face interviews. One- and two-way analyses were performed on the cost calculated. RESULTS: In 2008, the total cost of CHB infection and its complications was estimated to be around US$ 10 billion, with 80% contributable to direct medical cost. Antivirals were the major cost driver in treating CHB infections. The per-patient total annual direct medical cost increased with the severity of the disease with the cost amounted to US$ 943.64 for CHB and US$ 3,916.21 for hepatocellular carcinoma. Based on the results, if all Vietnamese patients received treatment for CHB infections, the estimated cost would be twice as much as the total health budget of Vietnam, highlighting that a significant proportion of CHB infections in Vietnam are not being treated, and the patients are bearing the extra cost out-of-pocket, or seeking treatment from traditional medicines. CONCLUSIONS: This study confirms that chronic HBV infection poses an unbearable financial burden for the average patient with a GDP per capita of around $1024, and the lack of access to treatment is a social issue in Vietnam. Although universal newborns vaccination against HBV has been implemented to reduce the number of infected subjects, more healthcare investment to improve access and provision of affordable medications by re-examining pharmaceutical policies to attain equity in proper treatment for patients with CHB infections would be needed.