The use of ozone using HealOzone technology allows the treatment of a vast range of dental caries at a very early stage and to induce lesion remineralisation from saliva. Such methodology has the potential to be the alternative to the conventional drilling and filling of dental caries. Objectives: The aim of this randomised, double blind clinical trial was to longitudinally monitor pit and fissure carious lesions (PFCLs) using light-induced fluorescence readings using a clinical classification of PFCLs as well as the DIAGNOdent (KaVo Germany), and to quantify the effects of Ozone application on these readings after six months. Methods: A total of 300 PFCLs were entered in 80 patients. After cleaning each lesion using air abrasion with 27.5 micron particles, a clinical severity index and DIAGNOdent (KaVo, Germany) standard scale readings were recorded. 220 lesions were treated at baseline with Ozone (using the HealOzone unit from CurOzone USA and KaVo Germany) for 20, 30 or 40 seconds according to their clinical severity, after one other lesion (receiving no Ozone) was randomised as control in each Patient. The clinical severity indices and DIAGNOdent readings were repeated after six months to evaluate changes on both the test and control lesions. Results: Ozone treated lesions clinically reversed (P<0.05) whilst control lesions did not change. A significant overall reduction of DIAGNOdent readings was associated with Ozone treatment after six months. The percentage of teeth which clinically reversed and produced this reduction was 85% (p<0.05). In contrast, the control lesions showed increased Diagnodent readings (P<0.05). Conclusion: The results demonstrate the effectiveness of Ozone to clinically reverse occlusal pit and fissure caries lesions and to also reduce their Diagnodent readings after six months.