Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the predominant pathogens associated with infections. MRSA infections have been associated with significant morbidity, mortality, and increased costs of care. Although colonization with MRSA is associated with a substantially increased risk for infection as well as transmission, decolonization of MRSA colonized hospital inpatients is not the standard of care. The standard strategy is to isolate the MRSA colonized patient and use contact precautions but not decolonize the patient. We know of no trials that have been conducted comparing the effectiveness of a standard isolation strategy with a decolonization strategy for both morbidity and transmission to household members post hospital discharge. We propose to compare the effectiveness of a standard patient isolation strategy without decolonization with a strategy of isolation and decolonization for hospital inpatients colonized with MRSA with respect to the following endpoints: A) reducing infection rates pre-discharge from the hospital among the index patients, B) reducing subsequent infections post-discharge among those without an infection in the index hospitalization, and C) reducing transmission of MRSA to household members post-discharge. This project is consistent with the informational goals of the Comparative Effectiveness portfolio at the Agency for Healthcare Research and Quality. We will conduct a randomized, double-blind, placebo-controlled trial among 918 adult (>20 years old) inpatients identified as colonized with MRSA through active surveillance at the Medical University of South Carolina Hospital. By using both randomization and a double-blind, placebo-control for mupirocin decolonization we are better assured that any differences between the two groups can be attributed to the addition of the active decolonization strategy. We will follow the index patients for 18 months post-discharge. In addition to assessing the development of infections pre and post-discharge from the hospital among the index patients and the transmission of MRSA from the index patients to their household members, we will also assess the development of mupirocin resistance that may result from the decolonization strategy. The implications of MRSA transmission and infection are substantial not only for morbidity and mortality in inpatient care but also for the community at large. A better understanding of the benefits and risks of MRSA decolonization in the hospital is essential to developing new methods for controlling the deleterious consequences of MRSA.