This investigation was designed to evaluate the healing response of 9.3-μm CO2 laser–assisted periodontal therapy. Five patients presenting with moderate to severe periodontitis, with an initial pocket depth (PD) ≥ 5 mm and with teeth predetermined to be surgically extracted, were enrolled and consented to treatment with full-mouth CO2 laser–assisted therapy. The laser treatment was carried out in the Ultraguide Mode at a setting of 0.25-mm spot size, with an average power of 0.65 to 1.15 watts and 20% mist. The laser tip was passed from the gingival margin and down apically to the base of the pocket with a sweeping L motion. The teeth were intensely scaled with piezoultrasonic instrumentation afterwards. A second pass of the laser tip was performed for the study teeth. At 9 months, all patients were clinically reevaluated. For sites with an initial pocket depth of ≥ 7 mm, a mean PD reduction of 3.97 ± 1.36 mm and a mean clinical attachment level gain of 3.54 ± 1.54 mm were achieved, resulting in a mean PD of 3.91 ± 0.77 mm. En bloc biopsy samples of four teeth were obtained and analyzed; two demonstrated histologic evidence of new bone formation while the other two healed with a long junctional epithelium with minimal inflammatory infiltrate. Further long-term clinical studies are needed to investigate the treatment stability obtained with a 9.3-μm CO2 laser compared to conventional surgical therapy. Nevertheless, the encouraging clinical results indicated that adjunctive use of the 9.3-μm CO2 laser–assisted periodontal therapy can be beneficial for treatment of periodontally compromised patients.