Non-surgical peri-implantitis therapies appear to be ineffective. Limited data suggest that ER:YAG laser therapy improves clinical conditions. The present study aimed at comparing the treatment effects between air-abrasive (AM) and Er:YAG laser (LM) mono-therapy in cases with severe peri-implantitis. Materials and methods Twenty-one subjects in each group were randomly assigned to one time intervention by an air-abrasive device or an Er:YAG laser. Clinical data were collected before treatment and at 6 months. Data analysis was performed using repeat univariate analysis of variance controlling for subject factors. Results No baseline subject characteristic differences were found. Bleeding on probing and suppuration decreased in both the groups (p < 0.001). The mean probing depth (PPD) reductions in the AM and LM groups were 0.9 mm (SD 0.8) and 0.8 mm (SD +/- 0.5), with mean bone-level changes (loss) of -0.1 mm (SD +/- 0.8) and -0.3 mm (SD +/- 0.9), respectively (NS). A positive treatment outcome, PPD reduction >= 0.5 mm and gain or no loss of bone were found in 47% and 44% in the AM and LM groups, respectively. Conclusions The clinical treatment results were limited and similar between the two methods compared with those in cases with severe peri-implantitis.