The incidence of bacteremia due to vancomycin-resistant Enterococcus (VRE) has increased markedly in recent years. We investigated the role of chloramphenicol in its treatment. All cases of VRE bacteremia occurring at our facility during a 45-month period were analyzed. The response to chloramphenicol, its effect on mortality, and the incidence of adverse effects were assessed. Fifty-one patients (65.4%) received chloramphenicol. Among patients in whom a response could be assessed, 22 (61.1%) of 36 demonstrated a clinical response, while 34 (79.1%) of 43 showed a microbiological response. Forty-two patients (53.8%) died as a result of the bacteremia. Although the mortality rate was lower for patients treated with chloramphenicol, the difference was not significant (odds ratio = 0.72; 95% confidence interval, 0.28-1.85; P = .49), nor was there an association between earlier initiation of therapy and reduced mortality (P = .45). In cases with central line-related bacteremia, there was no difference in mortality among patients treated with chloramphenicol, line removal, or both (P = .36). Although 16 patients (31.4%) had adverse effects, none could be definitely attributed to chloramphenicol. Although chloramphenicol was well-tolerated, no significant effect of its use on mortality could be demonstrated.