Effects of Intraoperative Ozone Application on Early Implant Stability: A Randomized Split-Mouth Clinical Trial

Background/Objectives: The aim of this study was to evaluate the effect of intraoperative gaseous ozone applied to the implant osteotomy immediately before implant placement on early implant stability using a split-mouth design and resonance frequency analysis (RFA). Methods: This prospective, randomized controlled split-mouth study included 40 patients receiving 106 implants in bilaterally symmetrical edentulous sites. Patients and outcome assessors were blinded. In the ozone group, ozone gas was applied to the implant site for 60 s immediately before implant placement; the control group underwent the same surgical protocol without ozone application. The primary outcome was the change in implant stability quotient from baseline to three months (ΔISQ). Secondary outcomes included baseline and three-month ISQ values, insertion torque, and postoperative pain assessed using a visual analog scale. Results: All 106 implants were analyzed. No significant between-group differences were observed in baseline ISQ (β = −0.49; 95% CI: −2.73 to 1.75; p = 0.668) or insertion torque (β = −0.62 Ncm; 95% CI: −1.96 to 0.72; p = 0.362). At three months, ISQ was higher in the ozone group (β = 1.91; 95% CI: 0.75 to 3.06; p = 0.001). ΔISQ was also significantly greater in the ozone group (β = 2.40; 95% CI: 0.34 to 4.45; p = 0.022; Cohen’s d = 0.42). Implant stability increased significantly in both groups (both p < 0.001). Postoperative pain did not differ between groups (β = −0.23; 95% CI: −0.83 to 0.36; p = 0.446). Although the effect direction was consistent across sensitivity analyses, ΔISQ was not statistically significant in the patient-level paired analysis (p = 0.089). No adverse events were reported. Conclusions: Intraoperative ozone application was associated with a modest increase in early implant stability without a significant difference in postoperative pain. However, given the small effect size and sensitivity of the findings to the analytical method, further large-scale, multicenter randomized controlled trials are required. Clinically, intraoperative ozone may be considered a potential adjunct to standard implant placement protocols, but the current evidence is insufficient to support its routine use.