Purpose: Tenofovir disoproxil fumarate (TDF) is a pregnancy category B antiviral, and is widely used in HIV mothers. However, data are lacking on its use in CHB mothers for the prevention of vertical transmission (VT). We investigated the safety of TDF use at the third trimester in mono-infected mothers with CHB. Methods: Data were retrospectively collected from chronic hepatitis B (CHB) mothers who received TDF (300 mg daily) at the third trimester from April, 2010 to January, 2013. Mothers with no antiviral treatment during pregnancy at the same period were included as controls. All infants received appropriated immunoprophylaxis. Primary endpoints were maternal or fetal complications and congenital defects/deformities at birth. Secondary endpoints included infants' HBsAg positivity beyond the age of 28 weeks and maternal postpartum adverse events (AEs). Results: Of 34 mothers enrolled, 26 received TDF, and 8 were controls, with their baseline values in Table 1. In the control group, maternal mean HBV DNA levels were lower than antiviral treatment in these mothers was rarely indicated. In the TDF-treated group, the mean (SD) fetal exposure to TDF was 7.3±2.57 weeks. Maternal complications, including preeclampsia (n=1) and prolong laboring (n=3), were reported in TDF-treated mothers, resulting in 15.38% (4/26) in TDF treated mothers vs. 0% of complications in controls (p=0.58). There was no TDF discontinuation due to AEs. At delivery, there was a significant reduction of maternal HBV DNA levels in TDF-treated mothers when compared to the control group (2.0 logs vs. 0 logs copies/mL, respectively; p=0.003). The mean HBV DNA in the TDF group was 5.37log10 copies/mL. There were 25 and eight infants born to TDF-treated mothers (one mother was not due yet) and mothers in the control group, respectively. There were no birth defects or congenital deformities observed in the entire cohort. The gestational age, infants' height/weight, or Apgar scores between the two groups were comparable. All infants in this cohort received timely immunoprophylaxis. Eight mothers discontinued TDF soon after postpartum (mean 6.17±3.92 weeks on TDF after delivery) with no severe hepatitis (ALT>10XULN or >5 x baseline). By the time of this abstract submission, nine infants in the TDF group, and four in the control group with age beyond 28 weeks had HBsAg tested, and all were negative.Table 1: Maternal baseline valuesConclusion: The use of TDF at the third trimester for highly viremic mothers was safe and well-tolerated, with a high successful rate on preventing vertical transmission. No congenital defects/deformities were observed at birth. TDF cessation during postpartum appears to be safe. A large prospective randomization trial is needed to verify our findings. Disclosure - Dr. Pan is a speaker and consultant for Gilead, other authors have none to disclose.