Purpose: To evaluate the clinical survival and impact on oral health–related quality of life (OHRQoL) of immediate loading of implant-supported full-arch CAD/CAM–milled PMMA interim restorations. Materials and Methods: This was a practice-based prospective cohort study performed in a Portuguese dental clinic. Eleven patients received a total of 17 CAD/CAM fully implant-supported, screw-retained, full-arch restorations with milled PMMA and were followed up for 1 year. The primary outcome was prosthesis survival, determined with a modification of the California Dental Association score and a Kaplan-Meier survival function analysis. The secondary outcome was the patient quality of life, as defined by application of the OHIP-14-PT questionnaire and standardized effect size variation between two visits. Significance was set at 5%. Results: Survival probability at 12 months was 76%, complete fracture of the prosthesis occurred in 17.6% of the cases, and small fractures without lab involvement occurred in 5.9% of cases. There was a significant improvement in OHRQoL between visit 1 and visit 4. The mean difference and effect size for total OHIP-14-PT score were –32.91 ± 3.68 and 3.66 (95% CI –1.83 to –5.80) respectively (P < .001* Wilcoxon matched paired rank test). Conclusions: Fullarch implant-supported CAD/CAM—milled PMMA interim prosthesis seem to be a viable approach with good survival rate and great impact on patient OHRQoL.