The aim of this study was to evaluate the effect of an ozone delivery system (HealOzone; KaVo, Biberach, Germany) in reducing dentin hypersensitivity. An 8-week, 3-visit, triple-blinded, randomized controlled clinical trial with 2 HealOzone machines (ozone/air) involving 44 subjects was conducted. The pain in response to tactile stimulus or desiccation was assessed by using a 100-mm visual analogue scale. Also, the global subjects' perception of sensitivity was assessed at each visit by using the visual analogue scale. No subjects reported an increase in pain or any adverse effect. All subjects reported a clinically significant reduction of pain at each follow-up relative to baseline; however, the difference between the study groups was not statistically significant. The effect of treatment of hypersensitive teeth with ozone reduces the pain sensation, but this effect cannot be distinguished from the placebo treatment. There was a large placebo effect that narrowed the range over which to detect treatment differences.