Purpose: The purpose of this study was to evaluate the clinical retention capabilities of a self-etch adhesive system (experimental group) and conventional acid-etch (control group) techniques and compare the caries incidence within six months and 24 months of follow-up periods. Methods: A total of 47 healthy children with a mean age of 9.7 years and either sound or noncavitated erupted permanent first molars were included in the trial. A total of 188 molars were randomly assigned in a split-mouth design for the self-etch mode in the universal adhesive or conventional acid-etch. Differences in sealant retention and caries incidence were compared at six and 24 months after sealant placement using a chi-square test. Results: Within 24 months of follow-up, the retention of fissure sealant applied using conventional acid etching (41 out of 66; 62.1 percent) was significantly higher (P<0.05) than that of the fissure sealant applied using self-etching mode in the universal adhesive system (17 out of 66; 25.8 percent). There was no significant difference in caries incidence between the two groups up to 24 months after sealant placement. Conclusion: With 24 months of follow-up, the retention of the conventional acid-etching technique were superior to those of the self-etch technique.