Objective: This study compared the ability, to resist toothbrushing abrasion, of two sealants formulated to prevent demineralization around orthodontic brackets. Methods: 25 human molars were sectioned mesiodistally into 50 tooth halves, each bearing either the buccal or lingual surface of a tooth. The samples were randomly assigned to two groups. Samples in Group 1 were painted with SeLECT Defense Enamel Surface Sealant (SD), while group 2 samples received Pro-Seal sealant. All sealants were applied in accordance with the manufacturer's instruction for clinical use. All samples were then subjected to toothbrushing with dentifrice slurry (1:4 toothpaste/water) using a programmable toothbrushing machine. All samples were brushed for a total of 20,000 strokes, the equivalent of 2 years of brushing, based on brushing twice daily at 13.7 strokes per surface per brushing. Each surface was brushed at a toothbrushing force of 2 N. Using Quantitative Light-induced Fluorescence device, the abrasion of the sealants from the tooth surface by toothbrushing was monitored after every 834 strokes (the equivalent of one month of brushing) for a total of 2,500 strokes (the equivalent of 3 months of brushing), then every 2,500 strokes for a total of 20,000 strokes. Removal of sealants was recorded as a percentage loss relative to the coated area, and compared between the two products at all time intervals using Bonferroni correction for multiple comparisons (α=0.05). Results: Within 1, 3, and 24 months, SD had an average loss of 10%, 23%, 37%, while Pro-Seal had 24%, 37%, 57%. The two treatments are significantly different (p=0.0015) at all time intervals. Conclusion: Both products were removed within the first one month of treatment; however SeLECT Defense was significantly more resistance to toothbrush abrasion than Pro-Seal. It may be suggested that while Pro-seal may require monthly re-application, SeLECT Defense may need only 3-monthly re-application.