Objective: To assess oral health-related quality of life (OHRQoL) changes before and after the primary surgical treatment in infants with cleft lip and/or palate (CL/P). Design: Quasi-experimental study. Methods: A total of 106 infants with CL/P younger than 2 years undergoing primary surgical treatment in the Plastic Surgery Service of the Instituto Nacional de Salud del Niño in Peru. The parent/caregiver answered a questionnaire about OHRQoL named the Peruvian version of the Early Childhood Oral Health Impact Scale (P-ECOHIS) in the pretreatment (baseline) and follow-up post-treatment. The total score of P-ECOHIS and their 2 sections (child impact and family impact) in the baseline and each follow-up period post-treatment scores were assessed. As well as, the type of the CL/P on OHRQoL, standardized effect sizes (ES) based on mean total change scores (difference between baseline and 12th month) were analyzed. Results: Improvements in infant’s OHRQoL after treatment were reflected in each follow-up period P-ECOHIS score compared to the baseline score. The total P-ECOHIS scores decreased significantly from 28.07 (baseline) to 7.7 (12th month; P <.0001), as did the individual domain scores (P <.0001). There were significant differences in the baseline and follow-up post-treatment scores of infants who reported improvement of the OHRQoL (P <.0001). The ES was large (3.79). The cleft lip had an improvement in the OHRQoL at 12th month post-treatment (P <.0001). Conclusions: Primary surgical post-treatment resulted in significant improvement of the infant’s OHRQoL with CL/P.