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To estimate and compare the direct medical cost in the management of chronic hepatitis B (CHB) infection and its complications from the perspective of public health organizations in Hong Kong and Singapore.Hong Kong and Singapore are endemic hepatitis B virus areas with about 10% and 5%, respectively, of the population estimated as hepatitis B virus infected.The medical histories of 660 patients with CHB who received medical services over 5 years from three major public hospitals in Hong Kong and Singapore were studied retrospectively. Costs were analyzed according to the five disease states and estimated in Hong Kong dollars (HKD) and Singapore dollars (SGD).In both Hong Kong and Singapore, the per-patient total annual cost increased with the severity of the disease. CHB cost HKD 6318 (U.S. $810) in Hong Kong and SGD 718.15 (U.S. $410.37) in Singapore. Compensated cirrhosis cost HKD 10,304 (U.S. $1321) in Hong Kong and SGD 1,175.34 (U.S. $671.62) in Singapore. Decompensated cirrhosis cost HKD 58,428 (U.S. $7490) in Hong Kong and SGD 15,389.84 (U.S. $8794.19) in Singapore. Hepatocellular carcinoma cost HKD 121,822 (U.S. $15,618) in Hong Kong and SGD 12314.04 (U.S. $7036.59) in Singapore. Each case of liver transplant was estimated to cost HKD 514,498 (U.S. $65,961) in Hong Kong and SGD 86,369.28 (U.S. $49,353.87) in Singapore. CHB in Hong Kong accounted for about 4% of the healthcare expenditure.This study confirms that CHB and its liver disease complications are a significant economic burden to the healthcare budgets of Hong Kong and Singapore, and indicates that effective therapy that arrests or reverses the progression of liver disease would be highly cost-effective.