The influence of dental treatment on oral health-related quality of life (OHRQOL) has rarely been evaluated in patients with intellectual disability (ID) through validated questionnaires. The aim of this study was to estimate the changes on OHRQOL in patients with ID after the implementation of an institutional dental treatment program under general anesthesia using the Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire (FHCOHRQOL-Q). A prospective longitudinal study was conducted on 85 patients (mean age=24.85 years) classified according to DSM-V whose parents/caregivers completed the FHC-OHRQOL-Q. We analyzed the changes in the questionnaire?s overall score and its dimensions from pre-treatment to 12-months of follow-up, considering effect sizes and minimal important differences estimated by the standard measurement error. The impact of clinical and therapeutic factors was evaluated using univariate and multiple linear regression analysis (p<0.05). Significant improvement of OHRQOL was found after dental treatment in oral symptoms (p0.001), daily life problems (p=0.018), parent?s perceptions (p=0.013) and FHCOHRQOL-Q´s overall score (p=0.001). OHRQOL changes exhibited an intermediate magnitude (0.38-0.21) as estimated by effect sizes. Changes in oral symptoms showed positive correlation with DMFT index (r=0.375, p=0.002), decayed teeth (r=0.244, p=0.036), dental extractions (r=0.424, p<0.001) and number of treatments (r=0.255, p=0.019). The improvement was greater in patients with 4 decayed teeth (p=0.049) and undergoing 2 dental extractions (p=0.002). Multiple regression analysis demonstrated that dental extractions (p<0.001) and DMFT index (p=0.028) were significantly related to oral symptom improvement. Dental treatment under general anesthesia showed a positive effect on the overall FHC-OHRQOL-Q score and most of its dimensions. At 12-months of follow-up, the improvement of oral symptoms was significantly associated with DMFT index, decayed teeth, dental extractions and number of treatments. In our clinical setting, the implementation of a dental treatment program enhanced the OHRQOL of patients with ID.