Both laser and fluoride have demonstrated inhibition on enamel demineralisation. Objectives: This study was aimed to compare the effectiveness of NaF/APF-Laser combined treatment and fluoride treatment alone on preventing enamel demineralisation. Methods: Five human non-carious molars were selected and covered with nail varnish leaving two windows on the buccal and lingual surfaces. The windows were randomly assigned to four treatment groups, including NaF, NaF-Laser, APF and APF-Laser groups. All windows received a 4-minute fluoride treatment before Er:YAG laser irradiation at an energy level of 8 J/cm2. The teeth were rinsed in deionised water for ten minutes before subjecting to a two-day pH cycling process. Longitudinal tooth sections (approximately 130±20μm thick) were cut and characterized using Polarised Light Microscope (PLM). The average lesion depths were measured and an ANOVA model was used to evaluate the preventive effects. Additionally, the morphology under the natural surface of each group was viewed with Scanning Electron Microscopy (SEM). Results: SEM characterisation revealed the significant increase of the intra-prismatic space in demineralised tissue. A decrease in lesion depth was found in fluoride-laser groups compared with fluoride groups (p<0.05). The effects of teeth (p=0.570) and topical fluorides (p=0.797) were not significant. Conclusions: The combined fluoride/laser treatment may provide additional preventive effects on enamel demineralisation compared with fluoride treatment alone. The type of topical fluorides, NaF or APF, does not affect its overall preventive effects. This project was supported by Singapore MOE grant R222-000-013-112 and BMRC grant R222-000-015-305 respectively.