Background: Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV in the 24 week therapy. The present study assessed the efficacy and viral resistance of 48 week clevudine therapy in patients with chronic hepatitis B. Method: A total of 42 patients (26 HBeAg positive and 16 HBeAg negative) who were received clevudine 30 mg once daily for 48 weeks were included in this analysis. Serum HBV DNA was quantified by real time PCR assay. Result: At week 48, median reductions of serum HBV DNA from baseline were 4.98 log10 IU/mL (5.00 log10 IU/mL for HBeAg positive and 4.95 log10 IU/mL for HBeAg negative) and 76.2% of patients showed undetectable serum HBV DNA (<60 IU/mL) (65.4% for HBeAg positive and 93.8% for HBeAg negative). The normalization of ALT levels (<35 IU/L) was achieved in 81.0% (88.5% for HBeAg positive and 68.8% for HBeAg negative). 15.4% of HBeAg positive patients showed HBeAg loss or seroconversion. HBV DNA negativity at week 48 was associated with HBeAg negativity (P =0.037), HBV DNA <2,000 IU/mL at weeks 4 and 24 (P =0.019 and 0.001, respectively). Two HBeAg positive patients showed viral breakthrough with M204I mutation during 48 week. Conclusion: Clevudine therapy in patients with chronic hepatitis B showed potent virologic responses at week 48, especially in those with HBeAg negativity and complete early virologic response (HBV DNA <2,000 IU/mL at weeks 4 and 24). But clevudine resistance can occur in HBeAg positive patients.