Background: NO-surgical peri-implantitis treatment modalities are unpredictable in their treatment outcome. A beneficial treatment might be the use of an air-polisher. In vitro studies show promising results in removing the biofilm without adversely affect the biocompatibility of the implant surface1,2,3. The clinical effect of air-polishing in the NO-surgical treatment of peri-implantitis is unclear since only a few studies have been performed4, mainly with small groups and various designs5. Aim/Hypothesis: The aim of this single-blINDIAd randomized controlled trial was to investigate the clinical, radiographical and microbiological effectiveness of air-polishing, with erythritol powder containing 0.3% chlorhexidine, in the NO-surgical treatment of peri-implantitis compared to ultrasonic debridement. Materials and Methods: Eighty patients (139 implants) with peri-implantitis (pocket depth (PD) ≥ 5 mm, marginal bone loss (MBL) ≥ 2 mm and bleeding and/or suppuration on probing (BoP/SoP)) were included and randomized into two groups. Test group patients were treated with an air-polisher (PERIOFLOW®, EMS) and erythritol powder (PLUS® powder). Control group patients were treated with an ultrasonic device (PIEZON®, EMS). Instruction on the additional use of interdental brushes with 0.12% chlorhexidine gel was given in both groups. The remaining dentition was cleaned using an ultrasonic device and/or hand instrumentation. The primary outcome was BoP (% of implant sites). Secondary outcomes were mean PD, SoP (%), plaque score (%), MBL and microbiological parameters. Examinations were performed at baseline and 3 months after therapy. Data were analyzed with SPSS statistical software. Results: Four patients were lost to follow-up, leaving 76 patients with 133 implants available for analysis. At 3 month evaluation, no significant differences were found between both groups for any of the clinical, radiographical and microbiological parameters. A significant reduction in BoP and PPD was found within both groups (BoP reduced from 59.5% to 49.8%, P = 0.011 in the test group compared to 56.0% to 48.1%, P = 0.051 in the control group; PPD reduced from 4.79 mm ± 1.19 to 4.38 mm ± 1.28, P < 0.001 in the test group compared to 4.98 mm ± 1.49 to 4.75 mm ± 1.78, P = 0.036 in the control group). No differences for plaque scores or SoP were found. Nor radiographical or microbiological differences were found within both groups. In 18% of all patients (14 patients (4 test/10 control) having 23 implants (5 test/18 control), treatment was considered so successful (no bleeding peri-implant pocket ≥ 5 mm) that no further surgical treatment was required at 3 month evaluation. Conclusions and Clinical Implications: NO-surgical peri-implantitis treatment using PERIOFLOW® (EMS) therapy with PLUS® powder (EMS) does not lead to improved clinical, radiographical or microbiological outcomes compared to PIEZON® (EMS) therapy 3 months after therapy. For a small amount of patients a NO-surgical treatment may be beneficial in such a way that no further surgical treatment is required. A surgical peri-implantitis procedure should therefore always be proceeded by a NO-surgical treatment phase. Keywords: Peri-implantitis, NO-surgical, Therapy, clinical trial, microbiology.