OBJECTIVE: To evaluate the efficacy of a comprehensive infection control program on the reduction of surgical-site infections (SSIs) following coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort study. SETTING: 1,000-bed tertiary-care hospital. PATIENTS: Persons undergoing CABG with or without concomitant valve surgery from April 1991 through December 1994. INTERVENTIONS: Prospective surveillance, quarterly reporting of SSI rates, chlorhexidene showers, discontinuation of shaving, administration of antibiotic prophylaxis in the holding area, elimination of ice baths for cooling of cardioplegia solution, limitation of operating room traffic, minimization of flash sterilization, and elimination of postoperative tap-water wound bathing for 96 hours. Logistic regression models were fitted to assess infection rates over time, adjusting for severity of illness, surgeon, patient characteristics, and type of surgery. RESULTS: 2,231 procedures were performed. A reduction in infection rates was noted at all sites. The rate of deep chest infections decreased from 2.6% in 1991 to 1.6% in 1994. Over the same period, the rate of leg infections decreased from 6.8% to 2.7%, and of all SSI from 12.4% to 8.9%. The adjusted odds ratio (OR) for all SSIs for the end of 1994 compared to December 31, 1991, was 0.37 (95% confidence interval [CI95], 0.22-0.63). For deep chest and mediastinal infections, the adjusted OR comparing the same period was 0.69 (CI95, 0.28-1.71). CONCLUSIONS: We observed significant reductions in SSI rates of deep and superficial sites in CABG surgery following implementation of a comprehensive infection control program. These differences remained significant when adjusted for potential confounding covariables.