ObjectiveThe purpose of this study was to determine factors predicting communication-related quality of life in children with cleft palate with or without cleft lip (CP ± L) or congenital velopharyngeal insufficiency (VPI).DesignCross-sectional design.SettingOutpatient pediatric craniofacial anomalies clinic.PatientsTwo-hundred and seventy-one children <18 years of age, diagnosed with CP ± L or congenital VPI.Main Outcome MeasureVelopharyngeal Insufficiency Quality of Life (VELO) scores as well as articulation, speech intelligibility, resonance, and voice outcomes were extracted from the electronic medical record in order to characterize communication-related quality of life. Total VELO score, as well as speech limitations, situational difficulty, emotional impact, perception by others and swallow subscores, were collected. Demographic factors, economic deprivation, medical history, and history of palatoplasty/pharyngoplasty were considered. Linear regression identified predictors of VELO total and subscores.ResultsPoorer speech intelligibility and increased hypernasality significantly predicted lower (worse) total VELO scores (P < .01), as well as more severe speech limitations (P < .01), situational difficulty (P < .01), emotional impact (P < .01), and perception by others (P < .01). The presence of glottal stop substitutions also predicted more severe emotional impact (P < .01). A comorbid behavioral health condition predicted significantly lower total VELO scores (P < .01), and children living in neighborhoods experiencing greater socioeconomic deprivation presented with worse swallow section scores (P < .01).ConclusionsHypernasality and decreased speech intelligibility primarily influenced the communication-related quality of life in children with velopharyngeal dysfunction. Additional research is warranted to determine how intervention can best mitigate VPI-related challenges in order to improve social interaction and quality of life.