Purpose: The primary objective of this study was to evaluate the safety of a tissue-engineered human ex vivo-produced oral mucosa equivalent (EVPOME) in intraoral grafting procedures. The secondary objective was to assess the efficacy of the grafted EVPOME in producing a keratinized mucosal surface epithelium. Materials and Methods: Five patients who met the inclusion criteria of having one mucogingival defect or a lack of keratinized gingiva on a nonmolar tooth, along with radiographic evidence of sufficient interdental bone height, were recruited as subjects to increase the width of keratinized gingiva at the defect site. A punch biopsy specimen of the hard palate was taken to acquire oral keratinocytes, which were expanded, seeded, and cultured on an acellular dermal matrix for fabrication of an EVPOME. EVPOME grafts were applied directly over an intact periosteal bed and secured in place. At baseline (biopsy specimen retrieval) and at 7, 14, 30, 90, and 180 days postsurgery, Plaque Index and Gingival Index were recorded for each subject. In addition, probing depths, keratinized gingival width, and keratinized gingival thickness were recorded at baseline, 30, 90, and 180 days. Results: No complications or adverse reactions to EVPOME were observed in any subjects during the study. The mean gain in keratinized gingival width was 3 mm (range, 3 to 4 mm). The mean gain in keratinized gingival thickness was 1 mm (range, 1 to 2 mm). No significant changes in probing depths were observed. Conclusion: Based on these findings, it can be concluded that EVPOME is safe for intraoral use and has the ability to augment keratinized tissue around teeth. Future clinical trials are needed to further explore this potential.