Methicillin-resistant Staphylococcus aureus was first identified in isolation in Europe during the 1960's. Now widespread throughout the world, infection with this organism has emerged as a major problem in surgical practice. However, it remains debatable whether MRSA is more virulent than methicillin-susceptible strains. We have reviewed our most recent 4-year experience of lower extremity amputations to examine the influence of MRSA and non-MRSA infection on clinical outcome. During the past 4 years, 165 patients underwent lower extremity amputation for SVS/ISCVS category III acute limb ischemia and grades II and III chronic limb ischemia. Forty-five had documented MRSA infection, while 57 patients had documented infection with other flora. All patients were treated with appropriate sensitivity-specific antibiotics and aggressive wound care. No significant differences were noted in the level of primary amputation required by the two groups. Similarly, no significant differences were noted in either number of revisions or revision to higher-level amputation, time to heal, hospital length of stay, or 30-day morbidity and mortality rates. Our results demonstrate that MRSA infection does not adversely affect clinical outcome in patients undergoing lower extremity amputations. Appropriate treatment of infections with sensitivity-specific antibiotics, thorough wound debridement, and aggressive wound monitoring should be routine in all patients, regardless of bacterial flora.