Background Limited evidence exists on the efficacy of regenerative treatment of peri-implantitis Materials and methods Subjects receiving antibiotics and surgical debridement were randomly assigned to placement of autogenous bone (AB) or bovine derived xenograft (BDX) with placement of a collagen membrane. The primary outcome was: evidence of radiographic bone fill and the secondary outcomes included reductions of probing depth (PD) bleeding on probing (BOP) and suppuration. Results 22 subjects were included in the AB and 23 subjects in the BDX group. Statistical analysis failed to demonstrate differences for 38/39 variables assessed at baseline. At 12 months, significant better results were obtained in the BDX group for bone levels (p < 0.001), BOP (p = 0.004), PI (p = 0.003), and suppuration (p < 0.01). When adjusting for number of implants treated per subject, a successful treatment outcome PD≤ 5.0 mm, no pus, no bone loss and BOP at 1/4 sites the likelihood of defect fill was higher in the BDX group (LR: 3.2, 95 % CI: 1.0 to 10.6, p < 0.05). Conclusions Bovine xenograft provided more radiographic bone fill than autogenous bone. The success for both surgical regenerative procedures was limited. Decreases in PD, BOP, and suppuration were observed.