ISSUE: Surgical site infections (SSIs) increase morbidity, mortality, cost, and length of stay. Studies support the use of antimicrobials to decrease the risk of SSIs. The National Surgical Care Improvement Project (SCIP) has defined optimal measures for surgical antimicrobial prophylaxis timing, selection and duration. A comparison among surgical subspecialty groups in a tertiary care academic hospital revealed a significant variance in the colorectal service compliance rate for optimal timing of antimicrobial prophylaxis. Colorectal service compliance rates for Jan-Mar, 2005 were 68% for optimal timing (within 1 hour of incision, or 2 hours for vancomycin) and 88% for selection. The rate for optimal duration (stopping ≤ 24 hours after surgery) for Apr-June was 30%. PROJECT: A multidisciplinary Colorectal SCIP Team was organized and utilized Six Sigma methodology to define, measure, analyze, and improve the surgical antimicrobial prophylaxis administration process. The goal was to increase compliance for all measures to 95%. The team created process flow and cause and effect diagrams. Analysis of process capability and variation were performed. The team implemented a process improvement plan that included: defining roles within the antimicrobial prophylaxis administration process; adding an antimicrobial prophylaxis question to the surgical time out; developing a SCIP education plan for stakeholders; revising colorectal pre/post-op order sets; and developing an electronic method for monthly feedback of rates to stakeholders. RESULTS: Colorectal service compliance rates for optimal timing of antimicrobial prophylaxis increased significantly during 2005: 1 st quarter (QTR) 68% (38/56) [Reference (Ref)], 2 nd QTR 92% (35/38) [RR 1.36], 3 rd QTR 92% (35/38) [RR 1.36], Oct-Nov 87%(13/15) [RR 1.28]. Chi-square test for trend 7.68, P 0.001. Colorectal rates for discontinuing antimicrobial prophylaxis within 24 hours after surgery increased significantly during 2005: 2 nd QTR 30% (10/33) [Ref], 3 rd QTR 61% (14/23) [RR 2.01], Oct-Nov 86% (12/14) [RR 2.83]. Chi-square test for trend 13.07, P LESSONS LEARNED: Six Sigma methodology was instrumental in identifying process barriers and focusing interventions to achieve an increase in the compliance rates of the surgical antimicrobial prophylaxis administration process.