This in vitro study compares a self-etch primer (SEP) to an etch-and-rinse (EaR) for bonding sapphire brackets by evaluation of the enamel etch-pattern, shear bond strength, amount of remnant adhesive and enamel surface damage following thermal and fatigue cyclic loading. Ceramic (sapphire) brackets were bonded to 80 extracted human premolars using two enamel etching protocols: conventional EaR using 37% phosphoric acid (PA) gel (control), and a SEP (Transbond Plus). Each group was subdivided into two subgroups (n=20 teeth) according to the time of bracket debonding: after 24 h water storage or following 5000 thermo-cycles plus 5000 cycles fatigue loading, to determine the shear bond strength (SBS), adhesive remnant index (ARI score), with scanning electron microscopy (SEM) evaluation of enamel condition. The control subgroups consistently exhibited significantly higher (p<0.05) SBS mean values (23.4-29.8 MPa) than the SEP subgroups (15.1-22.4 MPa) at both bracket debonding time points. However, the SEP subgroups yielded milder etch-patterns and attained SBS values above the minimum requirement range for clinical performance. In addition, the higher SBS of control subgroups was accompanied with higher ARI scores and enamel damage grades than SEP subgroups as confirmed by SEM. Thermocycling and fatigue significantly reduced the SBS of all subgroups, with a non-significant drop in the amount of adhesive residue or enamel damage. The use of SEP can be a suitable alternative to the conventional PA gel for sapphire bracket bonding as it maintains suitable bond strength and has the potential to produce both less remnant adhesive and enamel damage.