Objective:To compare the efficacy and safety of telbivudine (LDT) and tenofovir disoproxil fumarate (TDF) treatment during the second and third trimester in pregnant women with high viral load of hepatitis B virus (HBV).Methods:Totally 506 pregnancy women with HBV infection who received antiviral therapy during the second and third trimester of pregnancy in the obstetrical clinic of The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 1, 2016 to December 31, 2018 were retrospectively enrolled, and the anti-viral efficacy and safety in mothers and neonates were evaluated. Pregnancy women were divided into TDF group and LDT group according the medications. The efficacies including decline and negative rate of HBV DNA, the vertical transmission (VT) rate, the normalization rate of liver function in mothers between the two groups were compared. The safeties including birth weight of neonates, congenital deformities and the rates of preterm between the two groups were also compared. Chi-square test, independent sample t test or rank sum test were used for statistical analysis. Results:There were 239 pregnant women in the LDT group and 267 in the TDF group. The maternal HBV DNA levels before treatment in the LDT and TDF groups were (7.83±0.75) lg IU/mL and (7.82±0.66) lg IU/mL, respectively, while the maternal HBV DNA levels prior to delivery were 2.91(1.20) lg IU/mL and 2.83(1.01) lg IU/mL, respectively. The normalization rates of alanine aminotransferase (ALT) of chronic hepatitis B (CHB) pregnant women prior to delivery in TDF group and LDT group were 95.00%(38/40) and 98.18%(54/55), respectively. There were all no significant differences between the two groups ( t=0.097, U=1.040 and χ2=0.767, respectively, all P>0.05). For CHB pregnant women, the HBV DNA negative rate at one month postpartum in TDF group was 85.45%(47/55) and that in LDT group was 82.50%(33/40). The normalization rate of ALT in TDF group was 94.55%(52/55), and that in LDT group was 92.50%(37/40). There were no significant differences between the two groups ( χ2=0.152 and 0.164, respectively, P=0.697 and 0.687, respectively). The VT rates were 0(0/262) in TDF group and 0.43%(1/231) in LDT group, which had no significant difference between the two groups ( χ2=1.127, P=0.288). Two patients in LDT group who continued taking LDT 11 months postpartum switched to TDF because of HBV rt204 mutation, and no one had virus mutation in TDF group. No significant increased in creatine kinase in LDT group, and no significant abnormal calcium and phosphorus metabolism in the TDF group. The preterm rate was 7.87%(21/267) in TDF group and 4.18%(10/239) in LDT group, but there was no significant difference between the two groups ( χ2=2.970, P=0.085). However, the birth weight of neonates in TDF group ((3 204.72±490.50) g) was lower than that in LDT group ((3 374.31±467.50) g), and the difference was statistically significant ( t=3.780, P<0.01). During the course of treatment, no pregnant women discontinued treatment due to drug intolerance, and no infants presented with drug-related birth defects. Safeties for mothers and neonates were both good. Conclusions:Both LDT and TDF treatment could reduce the VT rate in pregnant women with high HBV viral load. The safety is good for both mothers and neonates. However, for CHB pregnant women who continue antiviral therapy postpartum, TDF is superior to LDT because of lower virus mutation, thus to reduce the risk of drug resistance.