The results of a case series of 51 consecutively treated, peri-implantitis-affected implants in 38 patients with follow-up measurements from 3 to 7.5 years are presented. Each implant displayed bleeding on probing, probing depths ≥ 6 mm, and bone loss ≥ 4 mm prior to surgery. A successful regenerative approach including surface decontamination, use of enamel matrix derivative, a combination of platelet-derived growth factor with anorganic bovine bone or mineralized freeze-dried bone, and coverage with a collagen membrane or a subepithelial connective tissue graft was employed in all cases. Patients were divided into two groups. Group 1 included patients in which the greatest defect depth was visible on radiographs; group 2 included patients in which the greatest loss of bone was on the facial or oral aspect of the implant. Bone level changes in patients in group 2 were determined by probe sounding under local anesthesia. Probing depth reductions at 3 to 7.5 years of follow-up were 5.4 and 5.1 mm in groups 1 and 2, respectively. Concomitant bone level gain was 3.75 mm in group 1 and 3.0 mm in group 2. No implant in either group lost bone throughout the duration of the study. The results to date with this regenerative approach for the treatment of peri-implantitis appear to be encouraging.