Purpose: Patients with skin-penetrating implants sometimes report episodic soft tissue reactions. This pilot clinical trial identified the oral microflora of the peri-implant sulcus of cancer patients with jaw reconstruction and compared sites with and without clinical signs of inflammation. Materials and Methods: Ten patients were selected during routine follow-up of their implant-supported removable prostheses. Eligible patients had at least two intraoral skin-penetrating implants; one showed clinical signs of inflammation with/without symptoms and the other served as a healthy control site. Eight of the 10 patients had undergone osseocutaneous fibula free flap reconstruction and two had received split-thickness skin grafts on the surface of the native mandible. Subjects were assessed on two visits, 30 to 40 days apart. Subgingival microbial samples were obtained and periodontal pocket depths were measured at the test implant abutment. Between visits, patients followed a strict oral hygiene regimen. Radiographic marginal bone loss around implants was measured using cone beam imaging during the second visit. The microflora were identified after isolation and purification of all growing colonies. Results: The number of different microorganisms ranged from 10 to 21 per site. Among all patients, a total of 47 different microorganisms were identified, but none were considered virulent red-complex periodontal pathogens. By the time of the second visit, after adherence to strict mechanical oral hygiene, the average number of microorganisms per site was reduced through elimination of some species. Almost all subjects had identical microbial species in both sites, but the number of visible colonies was lower at the healthy site. Conclusion: Oral peri-implant epidermal proliferation does not appear to be caused by specific microbial pathogens but is likely related to increased microbial load in the implant sulci. Mechanical oral hygiene improves and maintains healthier peri-implant skin tissues. Keywords: dental implants, jaw reconstruction, microvascular flaps, oral cancer, percutaneous implants, peri-implant disease, skin-penetrating implants, subgingival microflora