OBJECTIVES: To describe the conceptual framework and methodology of the Evaluation of Processes and Indicators in Infection Control (EPIC) study and present results of CVC insertion characteristics and organizational practices for preventing BSIs. The goal of the EPIC study was to evaluate relationships among processes of care, organizational characteristics, and the outcome of BSI. DESIGN: This was a multicenter prospective observational study of variation in hospital practices related to preventing CVC-associated BSIs. Process of care information (eg, barrier use during insertions and experience of the inserting practitioner) was collected for a random sample of approximately 5 CVC insertions per month per hospital during November 1998 to December 1999. Organization demographic and practice information (eg, surveillance activities and staff and ICU nurse staffing levels) was also collected. SETTING: Medical, surgical, or medical-surgical ICUs from 55 hospitals (41 U.S. and 14 international sites). PARTICIPANTS: Process information was obtained for 3,320 CVC insertions with an average of 58.2 (± 16.1) insertions per hospital. Fifty-four hospitals provided policy and practice information. RESULTS: Staff spent an average of 13 hours per week in study ICU surveillance. Most patients received nontunneled, multiple lumen CVCs, of which fewer than 25% were coated with antimicrobial material. Regarding barriers, most clinicians wore masks (81.5%) and gowns (76.8%); 58.1% used large drapes. Few hospitals (18.1%) used an intravenous team to manage ICU CVCs. CONCLUSIONS: Substantial variation exists in CVC insertion practice and BSI prevention activities. Understanding which practices have the greatest impact on BSI rates can help hospitals better target improvement interventions.