Abstract: Objective：To evaluate the effect and side effect of the antiviral regimens consisting of ganciclovir and/or valganciclovir on congenital cytomegalovirus (CMV) infected neonates. Methods：Retrospective analyze the data of neonates with congenital CMV infection hospitalized in the Newborn Department of the Children's Hospital of Fudan University from March 2012 to May 2017. The clinical characteristics, liver function, CMV DNA, brain MRI, fundus examination and treatment results of 3 groups were evaluated and compared. Results：Twenty-eight neonates were diagnosed as congenital CMV infection. Of whom, nine were asymptomatic or with mild symptoms and had not been treated with antiviral therapy; the remaining nineteen cases were congenital CMV infection with moderate or severe symptoms; among them, eleven cases were treated with ganciclovir and/or valganciclovir ≤6 weeks; and eight cases were treated with ganciclovir and/or valganciclovir for 6 months.① When followed up to 6 months old, except 1 patient had moderate elevated bile acid, all the other 27 had recovered symptoms and signs except the central nervous system, liver function and blood routine examination. ② In neonates with asymptomatic congenital CMV infection or with mild symptoms, a left hearing loss case emerged at 6 month. In ≤6 weeks antiviral group, 2 CMV-related fundus lesions healed in 1 month old; 3/5 patients still had abnormal brain MRI image and 2/5 patients had hearing loss when 6 months old. In 6 months treated group, all 4 fundus lesionsrelated to congenital CMV infection healed at the end of 6 months follow up, while 2/3 case still had abnormal brain MRI image and 1/7 with hearing loss.③ No statistical difference was observed in central nervous system symptom between 6 weeks group and 6 months group.④ No ganciclovir and/or valganciclovir related granulocytopenia and liver dysfunction occurred during follow-up. Conclusion：Treatments with ganciclovir and/or valganciclovir for ≤6 weeks or 6 months could improve senorineural hearing loss and chorioretinitis; while no significant difference regarding improvement of these lesions were observed between ≤6 weeks and 6-months treated groups at 6 month old. It is suggested that, neonates with asymptomatic congenital CMV infection should be screened by ophthalmoscopic examination, auditory brainstem response and MRI, early active antiviral therapy is recommended for neonate with emerging symptom.