Background: The aim of this study was to comparatively evaluate the effects of a universal adhesive system and a two-step self-etch adhesive system, applied in accordance with the manufacturers’ instructions and with sonic activation, on the microtensile bond strength (µTBS) to dentin. Materials and Methods: Forty caries-free human molars were randomly assigned to four experimental groups (n = 10) according to the adhesive system and application method (manufacturer’s instructions or sonic activation). A universal adhesive system (Nova Compo B Plus [NC]; Imicryl, Turkey) and a two-step self-etch adhesive system (Clearfil SE Bond [SE]; Kuraray, Japan) were evaluated. Each adhesive was applied either with a slight rubbing motion in accordance with the manufacturers’ instructions or with sonic activation. All teeth were restored with a composite resin compatible with the respective adhesive system. After storage in distilled water at 37°C for 24 hours, the specimens were sectioned into stick-shaped samples with a cross-sectional area of approximately 0.9 mm2. Microtensile bond strength testing was performed at a crosshead speed of 0.5 mm/min, and failure modes were evaluated under a stereomicroscope. The data were analyzed using two-way ANOVA followed by Tukey’s post hoc test (α = 0.05), and failure mode distributions were evaluated using the chi-square test. Results: Adhesive failures were observed in all groups. Sonic application significantly reduced the microtensile bond strength (µTBS) of the universal adhesive system compared with application according to the manufacturers’ instructions (P < 0.05). However, sonic activation did not produce a statistically significant effect on the dentin bond strength of the two-step self-etch adhesive system. Conclusion: The effect of sonic application on the microtensile bond strength (µTBS) to dentin appears to be dependent on the adhesive system used. While sonic activation adversely affected the bonding performance of the simplified universal adhesive system, it did not have a significant effect on the bond strength of the two-step self-etch adhesive system.