The purpose of this study was to evaluate the retention rates of a fissure sealant placed using different adhesive protocols over 24 months. Twenty-four subjects with no restorations or caries received fissure sealants (Clinpro Sealant, 3M ESPE) placed using different adhesive protocols. A total of 292 sealants were placed as follows by two previously calibrated dentists using a table of random numbers (n=73): group I, acid-etch/without adhesive; group II, with a self-etch adhesive (Adper Easy Bond, 3M ESPE); group III, with an etch-and-rinse adhesive (Adper Single Bond 2, 3M ESPE); group IV, with acid + self-etch adhesive (Adper Easy Bond). Two other calibrated examiners independently evaluated the sealants at baseline and at six-, 12-, 18-, and 24-month recalls. Each sealant was evaluated in terms of caries formation being present or absent and retention using the following criteria: 1 = total retention, 2 = partial loss, and 3 = total loss. Pearson's χ2 test was used to evaluate differences in retention rates among the sealants for each evaluation period. At the end of 24 months, total retention rates were 57.5%, 27.4%, 84.9%, and 76.7% in the acid-etch, self-etch adhesive, etch-and-rinse adhesive, and acid + self-etch adhesive groups, respectively. Although there were no statistically significant differences between the retention rates among the adhesive protocols at 6 months ( p=0.684), significant differences were observed at the 12-, 18-, and 24-month evaluations. At 24 months, the lowest retention rates were observed in the self-etch group ( p<0.05). No caries development was observed in any of the groups. The retention rate of sealants placed using self-etch adhesive was poor compared with the other groups.