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Background/aims: Although the natural seroclearance rate of Hepatitis B surface antigen (HBsAg) is reported to be 0.4-2% in western countries, this is not well known in Korea. This study aimed to elucidate the rate of natural HbsAg seroclearance, factors associated with seroclearance and prognosis after seroclearance., Methodology: In 1999, 250 chronic HBsAg carriers without any history of antiviral treatment and without any evidence of liver cirrhosis or hepatocellular carcinoma were selected. Follow-up HBsAg/ anti-HBs tests were performed annually till 2004. During a mean follow-up period of 48 months, 24 patients were lost and 11 received antiviral treatment. Finally, 215 patients completed the study., Results: HBsAg seroclearance was observed in 11 patients (6 males, 5 females). One-year seroclearance rate was 1.4%. All patients who achieved seroclearance were HBeAg (-)/HBV DNA (-) at the time of enrollment. Additionally, old age and normal serum alanine aminotransferase (ALT) level were the factors associated with seroclearance (p < 0.05, respectively). During the follow-up period, only mild transient elevations of ALT were observed in 4 patients and no serious complications were observed., Conclusions: Natural seroclearance occurred exclusively in patients who were HBeAg (-)/HBV-DNA (-), and annual rate of natural HBsAg seroclearance was 1.4%. No significant complications were observed after seroclearance.