This in vitro study determined the effect of enamel pretreatment with phosphoric acid and ethylenediaminetetraacetic acid (EDTA) on the bond strength of strong, intermediary strong, and mild self-etching adhesive systems. Ninety sound human premolars were used. Resin composite cylinders were bonded to flat ground enamel surfaces using three self-etching adhesive systems: strong Adper Prompt L-Pop (pH=0.9-1.0), intermediary strong AdheSE (pH=1.6-1.7), and mild Frog (pH=2). Adhesive systems were applied either according to manufacturer instructions (control) or after pretreatment with either phosphoric acid or EDTA (n=10). After 24 hours, shear bond strength was tested using a universal testing machine at a cross-head speed of 0.5 mm/minute. Ultra-morphological characterization of the surface topography and resin/enamel interfaces as well as representative fractured enamel specimens were examined using scanning electron microscopy (SEM). Neither surface pretreatment statistically increased the mean shear bond strength values of either the strong or the intermediary strong self-etching adhesive systems. However, phosphoric acid pretreatment significantly increased the mean shear bond strength values of the mild self-etching adhesive system. SEM examination of enamel surface topography showed that phosphoric acid pretreatment deepened the same etching pattern of the strong and intermediary strong adhesive systems but converted the irregular etching pattern of the mild self-etching adhesive system to a regular etching pattern. SEM examination of the resin/enamel interface revealed that deepening of the etching pattern was consistent with increase in the length of resin tags. EDTA pretreatment had a negligible effect on ultra-morphological features. Use of phosphoric acid pretreatment can be beneficial with mild self-etching adhesive systems for bonding to enamel.