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Introduction: Within the field of periodontology, there has been a proposal for the utilization of noninvasive laser therapy as a potential treatment for persistent periodontitis. The Laser-Assisted New Attachment Procedure (LANAP) employs an Nd:YAG laser as a specific technique. Through its interaction with endogenous chromophores, the Nd: YAG laser exhibits a selective effect on the evaporation of granulation tissue, therefore establishing a correlation with reduced bleeding. The study also examined Oxygen High-Level Laser Therapy (OHLLT). The OHLLT technique employs a high-power diode laser in combination with hydrogen peroxide solutions to facilitate the liberation of singlet oxygen, which possesses antibacterial attributes, within the periodontal pockets. The existing literature indicates their potential to promote the regeneration of tooth support tissues. Objective: The aim of this study is to assess the subjective pain levels reported by patients who have undergone surgery using the OHLLT protocol versus those who have undergone surgery using the LANAP technique. Methods: A total of 20 individuals with a stage III–IV periodontitis diagnosis were recruited for the study. The participants were randomly divided into two groups, each consisting of 10 individuals: Group 1, comprising patients treated according to the LANAP protocol, and Group 2, comprising patients treated according to the OHLLT protocol. After their initial session of nonsurgical periodontal therapy, individuals provided feedback regarding their level of pain, utilizing a Numerical Rating Scale (NRS) comprising time intervals of 0 h (T0), 6 h (T1), 12 h (T2), 24 h (T3), 48 h (T4), and 7 days (T5). The Wilcoxon–Mann–Whitney statistical test was employed to assess the variations in NRS scores between Group 1 and Group 2 at each recording period. (p ≤ 0.05). In addition, a microbiological assessment of the bacterial load in the periodontal region was conducted on all subjects using real-time PCR testing at two time points: prior to treatment (T0) and seven days post-treatment (T5). Results: The findings of this study indicate that the OHLLT group exhibited significantly lower pain levels compared to the LANAP group at all time intervals, except for the preoperative period, where no significant difference was observed (p < 0.05). Group 2 exhibited a more rapid decrease in pain, as demonstrated by a score test approaching zero within 24 h. The quantity of periodontal bacteria seen seven days post-treatment was similar between the two groups and was found to be decreased compared to the pre-treatment levels. Conclusions: The OHLLT and LANAP regimens have demonstrated efficacy in the nonsurgical management of periodontal disease. Nevertheless, it should be noted that the OHLLT approach does not subject the patient to any thermal hazards, unlike the LANAP method. The postoperative discomfort experienced following the OHLLT procedure is indeed reduced, as this technique is characterized by lower invasiveness and reduced dependence on the operator. [ABSTRACT FROM AUTHOR]