Objective: An evidence-based surgical antimicrobial prophylaxis (AMP) protocol was implemented in multiple facilities to determine if compliance led to a decrease in New York State reportable surgical site infections (SSIs). Implementation focused on changing practitioner behavior. Methods: An evidence-based protocol was developed and approved by participating clinical divisions in the five hospitals involved in the project. Quality assurance (QA) processes were established at each facility to promote compliance. One facility included repeated noncompliance with the protocol in physicians' QA profiles. Randomly selected clean and clean-contaminated procedures were retrospectively reviewed for patients discharged in 2001 (prior to AMP implementation) and 2003 (the implementation period). Trained nurses collected data on compliance with selection of the appropriate antibiotic, timing of administration, redosing, dose adjustment, and postoperative duration. Results: Compliance indicators improved at all facilities. Compliance with the combination of all five indicators improved from 11 percent to 34 percent (P < 0.001), and there was a nonsignificant decrease (3.0 percent vs. 2.5 percent; P = 0.22) in SSI rates. Conclusion:Compliance with an AMP protocol can be increased by implementing a multifaceted QA and educational process focused on changing physician behavior. Medical board oversight of noncompliance and inclusion in the physician QA profile seemed to be the most efficacious step in assuring physician compliance.