In HBV-infected pregnant women, there is a risk of perinatal HBV transmission even if the infant receives hepatitis B immunoglobulin and vaccine. In a multicentre phase III trial in Thailand, the use of the antiviral tenofovir to decrease maternal HBV load and improve the subsequent risk of perinatal transmission was evaluated. A total of 331 HBV-infected pregnant women were randomly assigned to receive either tenofovir (n = 168) or placebo (n = 163) from 28 weeks of gestation to 2 months postpartum, with HBV-positive status in the infant as the primary endpoint. None of the infants in the tenofovir group were infected with HBV compared with three infected infants in the placebo group, but the effect was statistically insignificant (P = 0.12). Adverse events did not differ significantly and the low levels of HBV transmission were attributed to efficacious timing of hepatitis B vaccinations in the infants.