Combination therapy with ampicillin, vancomycin, and gentamicin in vitro against several clinical isolates of vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium, including VanA and VanB strains, was evaluated. The MICs of ampicillin were not significantly decreased by induction with vancomycin, and the combination of ampicillin and vancomycin was not inhibitory for any strain. Triple-combination therapy was least active against highly resistant VanA isolates, achieving a reduction of less than 1 log CFU at 24 h, but demonstrated slightly more activity against VanB strains.