Fissure sealant is an important tool in the prevention of dental caries. This study evaluated the effect of treating the enamel with topical fluoride gel prior to acid etching on sealant retention clinically (Part I) and in vitro (Part II). In part I a split mouth design using contralateral first permanent molars was conducted. Seventy (35 pairs) molars were sealed. Fissure sealant was applied on one side of the mouth (control group) and the contralateral tooth received acidulated phosphate fluoride gel (test group) prior to acid etching. The sealant was evaluated after 6 and 12 months and scored as intact, partially lost or completely missing. In part II, the shear bond strength between sealant and buccal enamel of extracted permanent molars without or with topical fluoride treatment was evaluated. Results showed no statistically significant differences between the test and control groups either clinically or in vitro. It is concluded that topical fluoride application prior to acid etching does not have a deleterious effect on sealant retention. However, further investigations should be conducted using different types of fluoride before altering the traditional practices.