We describe a 66-year-old woman with infective endocarditis due to Cardiobacterium hominis whose condition, complicated by severe aortic regurgitation and congestive heart failure, necessitated aortic valve replacement despite treatment with ceftriaxone followed by ciprofloxacin. The blood isolate of C. hominis produced beta-lactamase and exhibited high-level resistance to penicillin (MIC, >==256 microgram/ml) and reduced susceptibility to vancomycin (MIC, 8 microgram/ml).