Abstract: Objective To investigate the influence of the sequence of PEG-IFNα-2 a and adefovir dipivoxil ( ADV) on the clinical outcome of patients with HBe Ag-positive chronic hepatitis B ( CHB) . Methods A total of 86 patients with HBe Ag-positive CHB who were treated in Yucheng People's Hospital from September 1, 2011 to November 1, 2013 were enrolled and randomly divided into groups A ( 28 patients, among whom one dropped out in the late stage) , B ( 29 patients, among whom two dropped out in the late stage) , and C ( 29 patients, among whom three dropped out in the late stage) . All patients were treated with PEG-IFNα-2 a combined with ADV; the patients in group A were given PEG-IFNα-2 a and ADV concurrently, those in group B were given PEG-IFNα-2 a for 24 weeks, followed by PEG-IFNα-2 a combined with ADV, and those in group C were given ADV for 24 weeks, followed by PEG-IFNα-2 a combined with ADV. The course of treatment was 60 weeks for all groups. The patients were followed up for 24 weeks after drug withdrawal. The three groups were compared in terms of clinical outcome [HBe Ag disappearance rate and seroconversion rate, HBs Ag clearance rate, HBV DNA clearance rate, and alanine aminotransferase ( ALT) normalization rate]. An analysis of variance or t test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Results After 60 weeks of treatment, there were significant differences in HBe Ag disappearance rate and seroconversion rate between the three groups ( 85. 2% vs81. 5% vs 69. 2%, χ2= 6. 253, P < 0. 05) , and groups A and B had significantly higher rates than group C ( all P < 0. 012 5) ; there was a significant difference in HBV DNA clearance rate between the three groups ( 81. 5% vs 55. 6% vs 80. 8%, χ2= 7. 409, P < 0. 05) , and groups A and C had a significantly higher rate than group B ( both P < 0. 012 5) ; there was a significant difference in ALT normalization rate between the three groups ( 81. 5% vs 80. 8% vs 57. 7%, χ2= 7. 425, P < 0. 05) , and group A had a significantly higher rate than group C ( P < 0. 012 5) . After 24 weeks of drug withdrawal, there were significant differences in HBe Ag disappearance rate and seroconversion rate between the three groups ( 81. 5% vs 81. 5% vs 65. 4%, χ2= 6. 723, P < 0. 05) , and groups A and B had significantly higher rates than group C ( all P < 0. 012 5) ; there was a significant difference in ALT normalization rate between the three groups ( 81. 5% vs 74. 1% vs53. 8%, χ2= 9. 690, P < 0. 05) , and group A had a significantly higher rate than group C ( P < 0. 012 5) . Most adverse reactions occurred within 24 weeks of treatment and mainly manifested as influenza-like symptoms such as low-grade fever, headache, and sore muscle, and most of the patients were relieved spontaneously without intervention. Some patients experienced bone marrow suppression manifesting as reductions in leukocytes, neutrophils, and platelets and were relieved after the treatment with granulocyte colony-stimulating factor. Conclusion ADV given at first to reduce HBV DNA and followed by the addition of PEG-IFNα-2 a can achieve a similar effect as ADV given concurrently with PEG-IFNα-2 a and has certain significance in shortening the duration of PEG-IFNα-2 a treatment and reducing the dose of PEG-IFNα-2 a.