Background: Oral health is now increasingly regarded as a crucial component of overall health and well-being. Fluoride varnish (FV) is thought to be safe, well-tolerated by children and simple to administer by health professionals for the prevention of dental caries. Since the year 2000, various reviews on the use of fluoride therapy in the prevention of dental caries have been published, but none on the frequency of fluoride varnish application. Hence aim of this systematic review is to evaluate the frequency of fluoride varnish application for prevention of dental caries in children. Objectives: To assess the effectiveness of frequency of fluoride varnish application in prevention of dental caries among preschool children. Methodology: Search Strategy: We searched the following databases for Randomized controlled trials (RCTs) in PubMed, Cochrane, Wiley, Proquest, Science Direct and Google Scholar which yielded 5657 articles. After screening the titles, 5657 articles were ruled out since they were unrelated to the systematic review’s goals. The remaining 75 articles were searched for duplication using Mendeley Software. Out of 75 articles, 12 articles were found to be duplicates. The remaining 63 articles were screened through abstracts and full text screening as next step. Out of 63 articles, 53 were excluded for various reasons like did not meet the inclusion criteria. Finally, 10 articles were qualitatively analyzed after which they were included in the systematic review and 6 in meta-analysis. Various key words included for screening were “Fluoride Varnish”, Dental Caries”, “Varnish Effectiveness” and “Frequency”. Extraction of the information and assessment of the methodological quality of the included studies using Risk of Bias was done by two authors (DV and RS). Meta-analysis using the random-effects model was conducted for the outcome (dmft score) after application of fluoride varnish. Mean difference (MD) or standardized mean difference (SMD) were used to estimate the effect, with 95% confidence intervals. Study Eligibility: All the studies published from January 2005 to April 2020, conducted among children between 0 to 5 years, articles published in English language were included. Studies conducted on animals, a review and a systematic review, participants aged above 5 years were excluded. Study appraisal and synthesis methods: Studies were assessed for quality with the help of pre-determined criteria which categorized the studies into high, medium and low quality. Random effect model was used for performing meta-analysis. Results: In total, 10 articles were included for qualitative synthesis. Various fluoride varnish and their frequency were assessed in the prevention of dental caries. All the studies had used Sodium fluoride varnish as a material however 3 studies have specifically mentioned the name, Durashield, Durafluor and Cavityshield respectively. Three studies have mentioned that they have applied fluoride varnish thrice in two weeks while rest of them have applied semiannually i.e.; once in every six months. The pooled overall cumulative mean difference of the dmft score after application of fluoride varnish was 2.67. Conclusion: Intensive application (Thrice in two weeks) of fluoride varnish gave better results when compared with semiannual application (Twice in a year) of fluoride varnish in preventing dental caries in preschool children.