Background: Few studies on speech performance of children after cochlear implantation (CI) described isolated large vestibular aqueduct syndrome (LVAS). Objective: To investigate speech developmental trajectories of infants with LVAS after CI, and to compare with those who have structurally normal inner ears. Materials and methods: 1112 infants with congenital severe to profound hearing loss participated in this study. 150 infants in group A were diagnosed with LVAS, 962 infants in group B with structurally normal inner ear. The speech performance was assessed via the Meaningful Use of Speech Scale (MUSS). The evaluations were performed pre-implant, 1, 3, 6, 9, 12, 24, 36, 48 and 60 months after CI. Results: The mean scores of the MUSS improved over a 5-year period after implantation in both groups A and B. The LVAS group presented similar speech developmental trajectory to the non-LVAS group at each assessment interval, except pre-operation. There were significant differences in mean scores between vocalizing behavior and oral communication skills, clarification skills of infants in both two groups.