Surveillance for catheter-related bloodstream infections (CRBSI) is hindered by the fact that clinical case criteria are complex and subjective. Simplified objective criteria, based only on microbiologic data, may be a less valid, but potentially more reliable system for estimating and comparing institutional infection rates. We developed an agent-based simulation model to examine the impact of these two different criteria on the measurement of CRBSI in a simulated 12-bed hospital intensive care unit (ICU). We found that, on average, the clinical criteria was more accurate at estimating the true CRBSI rate than the simple criteria (3.36+/-1.11 vs. 5.41+/-1.36 infections/1000 catheter-days, compared with a true rate of 3.54+/-1.60). However, ecologic correlation (i.e., the accurate ranking of CRBSI rates across institutions) was higher for simple criteria than clinical criteria. Thus, simplified objective criteria are potentially superior to clinical criteria in identifying the true differences in CRBSI rates between institutions.