BACkGrounD/oBJECtIvE: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is associated with a significant risk of subsequent MRSA infection in the hospital setting. The use of decolonization as an infection control strategy remains highly controversial despite publications evaluating more than 40 different decolonization regimens over the past 60 years. The present study describes the benefits and potential drawbacks of such an approach in the patient population. MEthoDs: A retrospective cohort study was performed to assess the efficacy and subsequent outcome for patients with newly identified MRSA colonization at the Horizon Health Network in Moncton, New Brunswick. rEsults: A total of 241 patients with MRSA colonization or infection during the study period (2000 to 2005 inclusive) were identified. Eighty-nine MRSA-positive patients were decolonized according to a standardized regimen (hospital protocol group), and 98 received an alternative decolonization regimen (other treatment group). No attempt at decolonization was made for 54 patients (no treatment group). The hospital protocol group demonstrated superior overall successful decolonization compared with the other treatment group (67 of 84 [80%] versus 48 of 89 [54%]; OR 3.3; 95% CI 1.6 to 7.1; P=0.0004) and the no treatment group (four of 43 [9%]; OR 36.9; 95% CI 11.2 to 161.7; P<0.000001). The mean observed duration of culture negativity for the subgroup who remained MRSA culture negative over the long term was 419±398 days (range one to 1817 days). Successful decolonization occurred in 115 patients and permitted subsequent release from contact isolation for 4530 patient-days. The rate of clinical infection with MRSA was significantly lower in the hospital protocol group versus the other treatment group (16 of 89 [18%] versus 37 of 98 [38%]; OR 0.38; 95% CI 0.18 to 0.78; P=0.003). ConClusIon:The present study supports recent reports indicating that MRSA decolonization can be successful using a multifactorial approach (chlorhexidine soap, enhanced hygiene/housekeeping and combination oral/topical antimicrobial therapy) in hospitalized patients, both over the short and long term. Unlike previous studies, decolonization appeared to be effective in a relatively unselected population, including patients with lines and catheters. Inability to decolonize was most closely associated with failure to use a standardized decolonization protocol.