OBJECTIVES: The purpose of this study was to evaluate a nonsurgical approach toward peri-implantitis by means of mechanical debridement and local detoxification leaving granulation tissue into the peri-implant pockets. MATERIALS AND METHODS: An analysis was performed on the outcomes of 2 nonsurgical protocols: mechanical debridement plus chemical detoxification with 0.2% chlorhexidine and chlortetracycline hydrochloride (test), and mechanical debridement alone (control). Measures were collected at baseline, 3, 24, and 36 months after treatment. RESULTS: Seventy-five implants with peri-implantitis were included. At a 36-month evaluation, mean pocket probing depth was 3.15 ± 0.32 mm for the test group and 5.97 ± 0.90 mm for the control group, the difference being significant. An improvement of marginal bone level was recorded for the test group, whether the control group showed a further marginal bone loss. Treatment success was 100% in the test group and 31.4% in the control group. CONCLUSION: Nonsurgical implant debridement alone seemed not efficient in the treatment of peri-implantitis. Further longitudinal studies are required to evaluate the efficacy of mechanical debridement with chemical detoxification and removal of granulation tissues against mechanical debridement with chemical detoxification alone.