Intramucosal inserts made of zirconia ceramic have been used for the rehabilitation of edentulous patients. This study aimed to follow up on patients with complete dentures having intramucosal zirconia inserts and to perform a histological analysis of biopsies of the epithelium surrounding the inserts. Twelve 31-66-year-old subjects of both genders received complete denture treatment having the intramucosal inserts in place. Detailed clinical, prosthetic and surgical procedures were described. Clinical exams were done on postoperative days 3, 7, 15, 120 and 360. One year after denture placement, the subjects received local anesthesia and the tissues surrounding the insertion sites in the alveolar ridge were removed using a scalpel blade. Biopsies were fixed for up to 48 h in 10% phosphate-buffered formaldehyde and 5-µm-thick sections were cut and stained with hematoxylin and eosin and Gomori Trichrome. Immunohistochemistry was used to identify endothelium (anti-CD3) and T lymphocytes (anti-CD31). Removing and reinserting the denture was painful until day 15, but all patients reported a marked increase in the retention and stability of the complete denture with little or no discomfort after 30 days. The histopathological analysis showed that zirconia inserts were well tolerated by the oral mucosa, with the presence of collagen fibers in the tissue around the insert, with mild inflammatory response and allowing reepithelialization, expressed by parakeratosis, epithelial hyperplasia and presenting granular layer. In conclusion, intramucosal zirconia inserts did not affect the health of oral mucosa and provide adequate retention and stability of the complete denture and comfort to the patients.