Introduction: Topical fluoride plays a vital role in the prevention of dental caries. Fluoride reduces enamel dissolution during acid attack.Laser irradiation also an adjunct to conventional caries prevention techniques. Objective: To compare __ampersandsignldquo;the effectiveness of__ampersandsignrdquo; diode __ampersandsignldquo;laser with__ampersandsignrdquo;Er:YAG laser on fluoride uptake of enamel surface using acidic and neutral topical fluorides. Methods: Enamel of each halved tooth specimens were painted with nail polish __ampersandsignldquo;varnish leaving a window__ampersandsignrdquo; of 5x5 mm of exposed enamel. One half of the sectioned tooth was taken as the control group, (n=40) and it__ampersandsignrsquo;s corresponding half as the experimental group (n=40). These two groups were further subdivided into 4 subgroups of 10 samples each depending upon the pH of topical fluoride and wavelength of the laser used. __ampersandsignldquo;Group A, Group B, Group C and Group D__ampersandsignrdquo; were marked as control groups and Group E, Group F, Group G and Group H marked as the experimental groups. Results: Fluoride ion-selective electrode and potentiometric analysis was used to calculate the mean fluoride uptake on the enamel surface of teeth. Er: YAG laser and diode laser after fluoride application on teeth demonstrated higher uptake of fluoride not only on enamel surface but also into the deeper structures. But, Er: YAG laser showed better results than diode laser for the incorporation of fluoride in teeth. Conclusion: APF-Er: YAG laser combination is most effective in the incorporation of fluoride in the teeth followed by NaF-Er: YAG, APF-Diode and NaF-Diode combination being the least.