In peri-implantitis, treatment lasers are effectively used to enhance implant surfaces’ decontamination of bacteria. The type of lasers commonly used and tested in dentistry are Nd:YAG, Er:YAG and diodes. The Er:YAG laser is considered to be effective in removing biofilm from implant surfaces. Photodynamic therapy (PDT), realized with low-level laser therapy (LLLT) and a photosensitizer, seems to have limited efficacy in peri-implantitis management, while diode lasers used with high frequency and power (Wiser, Doctor Smile), performed with hydrogen peroxide 10 vol. 3% (OHLLT), seems to lead to a deep sanitization of implant surfaces, without any thermal effect. The aim of our retrospective controlled study is to compare an oxygen high-level laser therapy (OHLLT) protocol with OHLLT with an Er:YAG laser (Pluser, Doctor Smile) in order to maximize bacterial removal and to evaluate if an Er:YAG laser could improve hard tissue regeneration with respect to OHLLT alone. Two hundred and ten implants affected by peri-implantitis were divided into two groups: 88 implants were treated with OHLLT alone (control group) while 122 underwent OHLLT and Er:YAG treatment (test group). Mean bone loss before (T0) and after treatment (T1) (with a follow-up of 5 years) was registered for all implants. The collected data were analyzed with the Statistical Package for Social Sciences (SPSS) version 11.5. No statistically significant differences were found. In the OHLLT group, we noticed a mean bone loss after treatment of 2.1 mm in the upper arch and 2.4 mm in the mandible. In the OHLLT + Er:YAG group, the results indicate a mean bone loss of 2.0 mm in the upper arch and 2.5 mm in the mandible. Both groups showed a mean bone loss after treatment of 2.3 mm. According to the Kolmogorov–Smirnov test, overall, data followed a normal distribution (value of the K-S test statistic = 0.0912; p = 0.36112). OHLLT plays a central role in enhancing clinical results in peri-implantitis treatment, leading to an effective bacterial decontamination. Our results showed no statistically significant differences between OHLLT and OHLLT + Er:YAG laser; thus, the potential advantageous role of Er:YAG has been downgraded with the analysis of our study.