The success of bonding brackets to enamel with resin bonding systems is negatively affected by contamination with oral fluids such as blood and saliva. The new self-etch primer systems combine conditioning and priming agents into a single application, making the procedure more cost-effective. The purpose of this study was to assess the effect of blood contamination on the shear bond strength of orthodontic brackets with a new self-etch primer. The brackets (precoated brackets APC II, 3M Unitek, Monrovia, Calif) were bonded to 52 extracted human molars according to 1 of 4 protocols. Group I: A self-etch acidic primer, Angel I (3M/ESPE, St. Paul, Minn), was placed on the enamel for 15 seconds, gently dried with air, and light cured for 10 seconds. Brackets were bonded and light cured for 20 seconds. Group II: The enamel surface was contaminated with human blood for 10 seconds, and the blood was blown off with an air syringe for 5 seconds. Angel I was applied on the contaminated surface; the brackets were then bonded and light cured as in group I. Group III: Angel I was applied as described in group I. The surface was then contaminated with human blood for 10 seconds, and the blood was blown off with an air syringe for 5 seconds. Precoated brackets were then bonded as in groups I and II. Group IV: The enamel surface was contaminated with human blood for 10 seconds and blown off with an air syringe for 5 seconds. The self-etch primer, Angel I, was applied as described earlier, and the surface was recontaminated with human blood for 10 seconds, and the blood was blown off with an air syringe for 5 seconds. The brackets were then bonded as in groups I, II, and III. The results of the analysis of variance (F = 13.31) indicated that the shear bond strengths of the 4 groups were significantly different (P =.001). Tukey HSD posterior tests indicated that the uncontaminated control group had a significantly stronger (mean = 6.0 +/- 3.5 megapascal [MPa]) shear bond strength than the groups that had blood contamination, regardless of whether this occurred before (mean = 2.7 +/- 2.4 MPa), after (mean = 1.1 +/- 0.6 MPa), or before and after (mean = 0.5 +/- 0.2 MPa) the application of the self-etch primer. Blood contamination at any stage of the bonding procedure results in a significant and drastic drop in the shear bond strength of orthodontic brackets.