Aims: To investigate clinical, radiographic and microbiological outcome over 12 months following open flap debridement of peri-implantitis with or without antibiotics. Materials and methods: Peri-implantitis was surgically treated with or without Zithromax® in 19 control and 20 test individuals. Probing pocket depth (PPD), gingival inflammation (BOP), intra-oral radiographs and microbial samples were studied. Per protocol and intent-to-treat analyses were performed. Results: The mean difference (reduction) in PPD values between baseline and month 12 in the test and control groups was 1.7 mm (SD ± 1.1, 95% CI: 1.1, 2.3, p <.001) and 1.6 mm (SD ± 1.5, 95% CI: 0.8, 2,4, p <.001), respectively. Data analysis failed to show study group differences for BOP, PPD, radiographic bone level and microbial load. Successful treatment (per protocol: PPD ≤ 5 mm, no BOP, no suppuration and no bone loss ≥0.5 mm) at 12 months in test and control groups was 7/15 (46.7%) and 4/16 (25.0%). Bacterial load reduction was similar in study groups with a temporary reduction following treatment. Conclusions: Surgical treatment of peri-implantitis with adjunctive systemic azithromycin did not provide 1-year clinical benefits in comparison with those only receiving open flap debridement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd