OBJECTIVE: To evaluate the long-term hearing outcomes of infants with symptomatic congenital cytomegalovirus (CMV) disease who received 16 mg/kg of oral valganciclovir (VGCV) twice daily for six months. STUDY DESIGN: We have currently performed a long-term extension study of an investigator-initiated, single-arm, prospective, multicenter clinical trial, in which 24 infants were treated with VGCV. Hearing outcomes up to three years after treatment initiation were described and the longitudinal changes in the proportion of "Improved hearing" were analyzed using logistic regression. The factors associated with these outcomes were explored. Adverse events that occurred after the completion of the administration period were assessed. RESULTS: At 3 years, among 48 ears from 24 infants, the number of "improved hearing," which was 19 (40.0 %) ears at 6 months, increased to 27 (56.3 %) ears (p = 0.032). When including "maintaining normal hearing" or "maintaining normal hearing or the same degree of hearing impairment", the corresponding numbers were observed in 35 (72.9 %) and 45 (93.7 %) ears at 3 years, which were 25 (52.5 %) and 45 (93.7 %) ears at 6 months, respectively. Infants with milder hearing impairment at baseline showed high likelihood of hearing improvement (p for trend = 0.018 by the regression analysis). No adverse events were observed after completion of the administration period. CONCLUSION: Oral administration of VGCV demonstrated efficacy in improving hearing in infants with symptomatic congenital CMV disease at 3 years of age. These results suggest that the treatment response may be particularly favorable in patients with a lower initial degree of hearing impairment.