Abstract: ob＜x＞jective To observe the efficacy and safety of oral valganciclovir (VGCV) in newborns with congenital cytomegalovirus infection. Methods The newborns with congenital CMV infection were divided into VGCV and GCV treatment groups. The VGCV treatment group cases were treated with oral valganciclovir ,16mg/kg, q12h; the GCV treatment group cases were intravenously injected with GCV, 6mg/kg, q12h. The course of treatment is 6 weeks. Blood and urine CMV-DNA PCR, serum CMV-IgM, hepatosplenomegaly, hyperbilirubinemia, cranial MRI, choroidal retinitis, brainstem auditory evoked potential, neutropenia were examined and compared between two groups. Nosocomial infection, PICC placement, length of stay, and hospitalization costs were compared between the two groups of patients. Results The VGCV group had similar effect to neonatal congenital cytomegalovirus infection, and the neutropenia occurred similarly during the treatment. VGCV group had significantly shorter hospital stay and lower cost. Hospital infection rate and PICC placement rate were lower than GCV group. Conclusion Oral valganciclovir is similar to intravenous ganciclovir in the treatment of neonatal congenital cytomegalovirus infection, and has similar adverse effects. It can shorten the length of hospital stay, reduce medical costs, the incidence of central venous catheterization and nosocomial infection.