Aim: To assess whether guided bone regeneration (GBR) treatment of peri-implantitis-related bony defects could improve healing compared to open flap debridement (OFD) at 36 months. Materials and Methods: In a multi-centre, randomized clinical trial, 32 individuals received OFD (control group [CG]) and 34 GBR treatment (test group [TG]). Radiographic defect fill (RDF), probing pocket depth (PPD), bleeding on probing (BOP) suppuration (SUP), mucosal recession (MREC) and patient-reported outcomes (PROs) were evaluated at 36 months. Results: Fifty individuals attended a supportive peri-implant therapy program and completed the 36-month follow-up. GBR treatment resulted in an RDF of 2.13 ± 1.26 mm compared to 1.64 ± 1.54 mm following OFD (p =.18). No difference was found in PPD, BOP, SUP, REC or PROs between the groups. Successful treatment (no additional bone loss, PPD ≤ 5 mm, no BOP and no SUP) was achieved in 46.2% in TG and 20% in CG (p =.053). Treatment results obtained at 12 months were generally maintained up to 36 months. No significant changes were noticed between 12 and 36 months. Conclusions: At 36 months, treatment results obtained at 1 year were sustained following both GBR and OFD in patients attending supportive peri-implant therapy. GBR resulted in more RDF and higher composite treatment success rate than OFD (ClinicalTrials.gov Identifier [NCT02375750]). © 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.