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OBJECTIVES The purpose of this experimental in vivo investigation was to evaluate the influence of modifying the implant surface by adding a monolayer of multi-phosphonate molecules on the development of experimental peri-implantitis. MATERIAL AND METHODS Eight beagle dogs received 5 tests and 5 control implants each following a split-mouth design 3 months after premolar and molar extraction. On the most mesial implant of each side, a 3-mm buccal dehiscence was artificially created. Experimental peri-implantitis was induced by silk ligatures over a 4-month period; after ligature removal, peri-implantitis was left to progress for another 4 months without plaque control. Clinical, histological, and radiographic outcomes were evaluated. RESULTS Radiographically, both implant groups showed a similar bone loss (BL) at the end of the induction and progression phases. BL measured on the histological sections of the test and control groups was 3.14 ± 0.42 mm and 3.26 ± 0.28 mm, respectively; the difference was not statistically significant (p > 0.05). The remaining buccal bone to implant contact (bBIC) percentage of the test and control groups was 59.38 ± 18.62 and 47.44 ± 20.46%, respectively; the difference, however, was not statistically significant (p > 0.05). Bone loss observed at dehiscent sites compared to non-dehiscent ones showed no statistically significant difference (p > 0.05). CONCLUSIONS Addition of a monophosphonate layer to a moderately rough implant surface did not affect development of experimental peri-implantitis. CLINICAL RELEVANCE Influence of implant surface on peri-implantitis may condition implant selection by the clinician, especially on patients with disease risk factors. In that sense, monophosphate layer implants do not show higher peri-implantitis risk than control implants.