Background and Objectives: The aim of the current study was to establish an osseo-disintegration model initiated with a single microorganism in mini-pigs. Materials and Methods: A total of 36 titanium dental implants (3.5 mm in diameter, 9.5 mm in length) was inserted into frontal bone (n: 12) and the basis of the corpus mandible (n: 24). Eighteen implants were contaminated via inoculation of Enterococcus faecalis. Six weeks after implant insertion, bone-to-implant contact (BIC) ratio, interthread bone density (ITBD), and peri-implant bone density (PIBD) were examined. In addition to that, new bone formation was assessed via fluorescence microscopy, histomorphometry, and light microscopical examinations. Results: Compared to the sterile implants, the contaminated implants showed significantly reduced BIC (p < 0.001), ITBD (p < 0.001), and PBD (p < 0.001) values. Around the sterile implants, the green and red fluorophores were overlapping and surrounding the implant without gaps, indicating healthy bone growth on the implant surface, whereas contaminated implants were surrounded by connective tissue. Conclusions: The current experimental model could be a feasible option to realize a significant alteration of dental-implant osseointegration and examine novel surface decontamination techniques without impairing local and systemic inflammatory complications.