We prospectively identified patients at the Massachusetts General Hospital from whom vancomycin-resistant enterococci (VRE) were isolated from a clinical specimen from 1 January 1991 through 31 December 1995. VRE strains were available from 139 (82%) of the 169 patients with clinical cases. Of these, 39 (28%) were identical or closely related by pulsed-field gel electrophoresis (i.e., VRE type A strain), including 38 (43%) of 89 VRE strains in 1995. By multivariate analysis, acquisition of the VRE type A strain was associated with receipt of clindamycin (odds ratio [OR] = 10.5), 15 or more days of hospitalization before the first isolation of VRE (OR = 2.9), and residence on one of the general medical floors (OR = 7.8). The VRE type A strain was a vanA strain of Enterococcus faecium and was highly resistant to all antimicrobial agents tested except chloramphenicol. These findings document the rapid dissemination of a highly resistant strain of E. faecium among patients and among other extant VRE strains at the Massachusetts General Hospital in 1995.