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AIM To answer the following PICOS question: In patients with peri-implantitis, what is the efficacy of surgical therapy with adjunctive systemic or local antimicrobials, in comparison with surgical therapy alone, in terms of pocket probing depth reduction, as assessed in randomized controlled trials (RCTs) with at least 6 months of follow-up? MATERIAL AND METHODS A systematic literature search was conducted. Reduction in mean probing pocket depth was the primary outcome. Secondary clinical outcomes were changes in suppuration (%), changes in bleeding on probing (%), marginal bone level changes (mm), disease resolution (%) and implant/prosthesis loss (%). Patient-reported outcome measures (PROMs), possible adverse effects and oral health related quality of life (OHRQoL) were also extracted if data was present. RESULTS 4 RCTs assessing the use of locally (2 RCT's) and systemically (2 RCT's) administered antimicrobial adjuncts to surgical treatment of peri-implantitis, with a 6 to 36 month follow-up were included. Seeing the substantial heterogeneity of interventions between the studies, meta-analysis could not be performed. A reduction in mean probing pocket depth was observed following all the involved surgical treatments, irrespective from the addition of antimicrobials. Except for the effect of systemic antimicrobials on marginal bone level changes and local antimicrobials on BOP, the effect of systemic and local antimicrobials was equivocal for all secondary outcome measures. CONCLUSIONS Based on the limited available evidence, the adjunctive use of the currently tested systemic or local antimicrobials during surgical therapy, in comparison with surgical therapy alone in patients with peri-implantitis does not seem to improve clinical efficacy. With regard the use of systemic antimicrobials, only 50% of the cases would show disease resolution after 1 year. There is a lack of studies that consider the sole use of local antimicrobials. Therefore, their true effect remains unclear. This article is protected by copyright. All rights reserved.