Background: To define the best timing for the treatment of high maternal viral DNA levels in order to block the mother-to-child transmission (MTCT).Methods: From a total of 820 HBsAg-positive pregnant women, 229 who satisfied the selection criteria were enrolled for the final analysis. These patients were divided into thress groups: Group A: 62 patients received telbivudine (LdT) (600 mg/day, orally) treatment before pregnant; Group B: 101 patients received LdT treatment at 24-28 weeks of gestation; and Group C: 66 patienst with high viral load received LdT at the third trimester. All infants born to the enrolled women were vaccinated with 100 IU of hepatitis B immune globulin (HBIG) and 10 μg of hepatitis B vaccine within 2 hours of birth. The second and third does of recombinant HBV vaccine were administered at 1 and 6 months of age, respectively.Results: LdT can effectively reduce serum HBV DNA and normalize ALT levels before delivery (p<0.001). The HBsAg positivity rate in infants in Groups A, B and C after delivery was 1.6%, 7.9% and 3.0%, respectively. The serum HBV DNA positivity rate in infants in Groups A, B and C after delivery was 4.8%, 5.0% and 0%, respectively. After 28 weeks of follow up, all infants remained HBV DNA and/or HBSag negative. No serious adverse events were found in the mothers or their infants treated with LdT.Conclusions: Telbivudine (LdT) given at the 28-32 weeks of gestation can effectively reduce mother-to-child transmission in HBV-infected women with good safety.