Our ICU-level analysis has several limitations. First, estimating cross-transmission frequency by molecular studies to determine the genetic relatedness of all VRE isolated from participating ICUs was beyond the scope of this study. Therefore, our model lacks a factor to account for cross-transmission of epidemic strains in any particular ICU; such transmission may explain some of the variation observed in the data, and the role of such transmission relative to antimicrobial use cannot be directly assessed from our data. However, to better address this, we did contact all ICUs that reported higher (top 90th percentile) rates of VRE, and none reported an outbreak of VRE in their ICU. Second, no standardized severity-of-illness measure was used in our comparisons (22–23). However, we could include the type of ICU and status of major teaching center as proxy measures for case mix. Furthermore, we suspect that the average length of stay and rates of device use in a given ICU are proxy measures for severity of illness, although these factors were not significant in the multivariate model. Third, our analysis of pooled data over a study period did not evaluate a possible temporal association between specific antimicrobial use and VRE; this evaluation will be possible in a future analysis after receipt of additional data. Finally, our study was of an ecologic nature and did not include collection of data on patient-specific exposures or risk factors or on specific clinical outcomes regarding infection, treatment, or mortality associated with VRE. While ecologic studies have several practical advantages, their lack of individual-level data limits the extent to which causal inferences can be drawn and makes control of confounding more challenging (24). On a related issue, we did not ascertain the clinical relevance of the isolates. However, we have analyzed these and related data from the ICU component of the National Nosocomial Infections Surveillance System and have determined that the aggregated susceptibility data from isolates reported in Project ICARE (including the data in this study) accurately reflect the resistance prevalence related only to isolates associated with hospital-acquired infections (25). Despite such limitations, our data demonstrate an association between the rates of use of some antimicrobial agents and rates of antimicrobial resistance at an institutional level for 60 hospitals. These findings are supported by those of single-institution studies that used patient-level analysis (1, 5, 7).