Objective. To evaluate the use of inpatient pharmacy and administrative data to detect surgical site infections (SSIs) following hysterectomy and colorectal and vascular surgery. Design. Retrospective cohort study. Setting. Five hospitals affiliated with academic medical centers. patients. Adults who underwent abdominal or vaginal hysterectomy, colorectal surgery, or vascular surgery procedures between July 1, 2003, and June 30, 2005. Methods. We reviewed the medical records of weighted, random samples drawn from 3,079 abdominal and vaginal hysterectomy, 4,748 colorectal surgery, and 3,332 vascular surgery procedures. We compared routine surveillance with screening of inpatient pharmacy data and diagnosis codes and then performed medical record review to confirm SSI status. Results. Medical records from 823 hysterectomy, 736 colorectal surgery, and 680 vascular surgery procedures were reviewed. SSI rates determined by antimicrobial- and/or diagnosis code-based screening followed by medical record review (enhanced surveillance) were substantially higher than rates determined by routine surveillance (4.3% [95% confidence interval, 3.6%-5.1%] vs 2.7% for hysterectomies, 7.1% [95% confidence interval, 6.7%-8.2%] vs 2.0% for colorectal procedures, and 2.3% [95% confidence interval, 1.9%-2.9%] vs 1.4% for vascular procedures). Enhanced surveillance had substantially higher sensitivity than did routine surveillance to detect SSI (92% vs 59% for hysterectomies, 88% vs 22% for colorectal procedures, and 72% vs 43% for vascular procedures). A review of medical records confirmed SSI for 31% of hysterectomies, 20% of colorectal procedures, and 31% of vascular procedures that met the enhanced screening criteria. Conclusion. Antimicrobial- and diagnosis code-based screening may be a useful method for enhancing and streamlining SSI surveillance for a variety of surgical procedures, including those procedures targeted by the Centers for Medicare and Medicaid Services.