The aim of this study was to evaluate the efficacy of therapeutic ozone application in the management of pain, swelling, and trismus associated with the surgical removal of impacted mandibular third molars. Sixty consecutive patients with asymptomatic bilateral impacted mandibular third molars were recruited into the study. Randomly, by use of envelops, the molar on one side was extracted and ozone therapy was given (study side); the molar on the other side was extracted 2 weeks later and sham ozone therapy was given (negative control side). The mean age of the 60 patients was 22.6 +/- 2.3 years (range 18-25 years). No differences were found between the two sides for mouth opening or swelling. The degree of pain and the number of analgesic tablets taken was significantly lower for the study side. This study showed ozone therapy to have a positive effect on OHIP-14 questionnaire results.