The optimal oral antimicrobial prophylactic regimen for bone marrow transplant recipients remains to be elucidated. We randomized 84 patients to receive either oral ciprofloxacin or ciprofloxacin plus vancomycin at hospital admission. Patients were monitored for bacteremias and clinical parameters, and stool and throat swab surveillance cultures were performed. The addition of vancomycin resulted in a significant decrease in the frequency of patients with surveillance cultures positive for coagulase-negative staphylococci (stool cultures, 44 versus 23%; throat swab cultures, 37 versus 19%) and alpha-hemolytic streptococci (throat swab cultures, 90 versus 60%). The frequencies of positivity for Candida spp. and gram-negative organisms on surveillance cultures were comparable. Despite these results, no differences in the incidences of bacteremias (12 of 41 versus 12 of 43 patients) or clinical parameters such as number of days to first fever, total number of febrile days, length of stay, and number of transfusions could be demonstrated. Because of a lack of efficacy of vancomycin and emerging problems with vancomycin-resistant isolates, vancomycin should not be used in oral antimicrobial prophylaxis regimens.