Patients who are colonized with enteric vancomycin-resistant Enterococcus faecium (VREF) are a major reservoir for transmission of and infection with this organism. In a randomized, controlled study to assess the effectiveness of high-dose bacitracin in the eradication of enteric VREF, 12 patients who were colonized with VREF were randomized to receive placebo (n=6) or orally administered zinc bacitracin (n=6) for 10 days. Posttreatment perirectal or stool cultures indicated that after 3 weeks, VREF had been eradicated from the stool of only 2 (33%) of 6 patients in each group. Of the 8 remaining patients who were still VREF-positive at 3 weeks after treatment, 5 (62%) had later evidence of spontaneous enteric eradication at 8 weeks. Further testing of VREF isolates revealed that a significant number (n=22, 76%) were resistant to bacitracin and that patients may have been colonized with multiple different VREF strains. Although bacitracin was not effective in the enteric eradication of VREF, the high rates of spontaneous eradication suggest that other host and environmental factors are more important in achieving long-term suppression or elimination of VREF colonization.