Purpose: This study introduces a newly developed zirconia complete denture (ZrD) that incorporates a ceria-stabilized zirconia/alumina nano-composite framework fabricated with computer-aided design/computer-aided manufacture (CAD/CAM). Materials and Methods: Twenty-nine edentulous patients received either a maxillary ZrD (n = 10) or a maxillary conventional complete denture (CD) (n = 19). Patient satisfaction was evaluated before and 12 months after prosthesis placement using the McGill Denture Satisfaction Instrument. Results: During follow-up periods of up to 2 years, no denture fractures were found in the ZrD or CD group. All aspects of patient satisfaction improved, and no significant group differences were found. Conclusion: Within the limitations of this study, it can be concluded that maxillary complete dentures with nano-zirconia frameworks might be an alternative prosthetic treatment option.