The current trend towards minimum-intervention dentistry has introduced laser technology as an alternative technique for cavity preparation. This study assessed the null hypothesis that enamel prepared either by Er,Cr:YSGG laser or conventional diamond bur is equally receptive to adhesive procedures. The buccal and lingual surfaces of 35 sound human molars were prepared with Er,Cr:YSGG laser or a medium-grit diamond bur. One etch&rinse (OptiBond FL) and three self-etch adhesives (Adper Prompt L-Pop, Clearfil SE Bond and Clearfil S3 Bond) were applied on laser-irradiated and bur-cut enamel, followed by the application of a 5-6 mm build-up of Z100. The micro-tensile bond strength (microTBS) was determined after 24 hours of storage in water at 37 degrees C. Prepared enamel surfaces and failure patterns were evaluated using a stereomicroscope and a field-emission-gun scanning electron microscope (Feg-SEM). The pTBS to laser-irradiated enamel was significantly lower than to bur-cut enamel (p<0.05), with the exception of Clearfil S3 Bond, which bonded equally effectively to both substrates. The latter presented the highest microTBS on laser-irradiated enamel, though it was not statistically different from the microTBS of OptiBond FL. SEM analysis revealed significant morphological alterations of the laser-irradiated enamel surface, such as areas of melted and recrystalized hydroxyapatite and deep extensive micro-cracks. In conclusion, the bonding effectiveness of adhesives to laser-irradiated enamel depends not only on the structural substrate alterations induced by the laser, but also on the characteristics of the adhesive employed.