The aim of the present study was to evaluate the effect of the application of a hydrophobic resin on the microleakage of Cl V composite resin restorations using a universal adhesive system applied in the self-etch (SE) and etch-and-rinse (ER) modes. Cl V cavities were prepared on the buccal surfaces of 64 human premolar teeth and divided into four groups (n = 16): ER, ER with hydrophobic resin (ERH), SE, and SE with hydrophobic resin (SEH). Microleakage at occlusal and gingival margins was evaluated using 0.5% methylene blue dye penetration technique under stereomicroscope at 40 × magnification. Data were analyzed using Kruskal-Wallis and Mann-Whitney U-tests (P < 0.05). At the enamel margins, the ER group had significantly less microleakage than the SE and SEH groups (P < 0.001), but had no significant difference compared with the ERH group (P > 0.05). There was also no statistically-significant difference between the SE and SEH groups (P > 0.05). At the dentinal margins, the SE group had significantly less microleakage compared with the ER (P < 0.001) and ERH groups (P = 0.005). Furthermore, microleakage of the SEH group was significantly less than the SE group (P < 0.001). Applying an extra layer of hydrophobic resin significantly decreased microleakage in the SE mode at the dentinal margin, but had no significant effect in the ER mode.