The aim of this in vitro study was to compare the microleakage of Er:YAG laser and diamond bur on different bonding systems in class V restorations. Class V cavities were prepared with Er:YAG laser or diamond bur on 80 intact human molars. Teeth were randomly distributed into ten groups and cavities were restored with CeramX duo (DENTSPLY) or Filtek Silorane (3M/ESPE) using different bonding materials (One Coat 7.0 (ColtSne), XP Bond (DENTSPLY), Clearfil Protect Bond (Kuraray), AdperSE (3M/ESPE), and Silorane System Adhesive (3M/ESPE). All specimens were subjected to thermocycling and load cycling. After being immersed in silver nitrate dye, the specimens were sectioned. Microleakage was evaluated by stereomicroscope and SEM. Data were statistically analyzed by one-way ANOVA, Kruskal-Wallis, and Mann-Whitney tests. Statistically differences were found between groups (p > 0.05) and cavities prepared with the Er:YAG laser showed higher microleakage than diamond bur. The microleakage of different bonding systems was influenced by the choice of diamond bur or Er:YAG laser for class V composite cavity preparation.