This systematic review and meta-analysis shows that valacyclovir administered to pregnant women with cytomegalovirus (CMV) infection reduces the risk of congenital CMV infection and increases the likelihood of infection being asymptomatic. However, no evidence of significant improvement of other CMV-related adverse perinatal outcomes was found. What are the clinical implications of this work?Prenatal valacyclovir administration should be considered when first-trimester maternal CMV infection is suspected on serology, while more evidence is needed to support its use once fetal infection has been confirmed.