Abstract: Objective To evaluate the clinical efficacy and safety of telbivudine( TLD) and interferon( IFN) α in the treatment of HBe Ag-positive chronic hepatitis B( CHB). Methods A total of 84 CHB patients who were admitted to Xiamen Municipal Third Hospital Affiliated to Fujian University of Traditional Chinese Medicine from April 2011 to October 2013 were equally and randomly divided into TLD group( treated with TLD) and IFNα group( treated with IFNα). Serum alanine aminotransferase( ALT) normalization rate,HBV DNA clearance rate,HBe Ag seroconversion rate,the quantity of HBe Ag,and the safety of the two drugs were determined at weeks 12,24,and 48 of treatment. Comparison of continuous data between the two groups was made by independent- samples t test,and comparison of categorical data was made by chi- square test. Results There were no significant differences in serum ALT normalization rate between the two groups at weeks 12,24,and 48 of treatment( P > 0. 05),and there were no significant differences in HBe Ag seroconversion rate between the two groups at weeks 12 and 24 of treatment( P > 0. 05). The TLD group had a significantly lower HBe Ag seroconversion rate than the IFNαgroup at weeks 48 of treatment( χ2= 4. 42,P = 0. 04). And the TLD group had a significantly higher HBV DNA clearance rate than the IFNα group at weeks 12( χ2= 4. 53,P = 0. 02),24( χ2= 7. 16,P = 0. 01),and 48 of treatment( χ2= 5. 19,P = 0. 03). The IFNα group had a significantly lower quantity of HBe Ag than the TLD group at week 48 of treatment( t = 2. 45,P = 0. 02). No obvious adverse reactions were found in either group. Conclusion For patients with HBe Ag- positive CHB,TLD has a strong antiviral effect and leads to a higher HBV DNA clearance rate than IFN at weeks 12,24,and 48 of treatment,but it causes a lower HBe Ag seroconversion rate than IFN at week48 of treatment. Both drugs have good safety and tolerability.