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Background and purpose: Enamel demineralization around orthodontic brackets is a significant problem. This study aimed to compare the efficacy of Casein phosphopeptide amorphous calcium phosphate (CPP-ACP) varnish and fluoride varnish in preventing enamel demineralization around and beneath orthodontic brackets. Materials and methods: Twenty extracted premolars were randomly divided into two groups and orthodontic brackets were bonded to their buccal surface by composite. The amount of fluorescent light reflected back from the enamel at the mesial and distal of the bracket was measured using a DIAGNOdent™ pen. MI varnish (CPP-ACP) was applied on the exposed enamel of the distal half of the teeth in group I while FluoroDose varnish was applied on the same area in group II. The mesial half of the teeth served as the control group. All teeth underwent two demineralization cycles and after each cycle, enamel demineralization was quantified at mesial and distal areas (T1, T2). The brackets were then debonded, and area under the brackets was also measured by DIAGNOdent™ pen (T3). Data were analyzed using repeated measures ANOVA and paired t-test. Results: In both groups, significant difference was noted between the mesial and distal areas in degree of demineralization at T2 (P