A case-control study was conducted to determine the modifiable risk factors associated with vancomycin-resistant Enterococcus (VRE) colonization during a hospital outbreak. Cephalosporin use was identified as the only independent risk factor (odds ratio, 13.8; 95% confidence interval, 2.5-76.3; P = .01). Nursing work-load intensity was not associated with VRE colonization in this study.