Screening for methicillin-resistant Staphylococcus aureus (MRSA) in high-risk patients is a legislative mandate in 9 US states and has been adopted by many hospitals. Definitions of high risk differ among hospitals and state laws. A systematic evaluation of factors associated with colonization is lacking. We performed a systematic review of the literature to assess factors associated with MRSA colonization at hospital admission.We searched MEDLINE from 1966 to 2012 for articles comparing MRSA colonized and noncolonized patients on hospital or intensive care unit (ICU) admission. Data were extracted using a standardized instrument. Meta-analyses were performed to identify factors associated with MRSA colonization.We reviewed 4,381 abstracts; 29 articles met inclusion criteria (n = 76,913 patients). MRSA colonization at hospital admission was associated with recent prior hospitalization (odds ratio [OR], 2.4 [95% confidence interval (CI), 1.3-4.7]; P < .01), nursing home exposure (OR, 3.8 [95% CI, 2.3-6.3]; P < .01), and history of exposure to healthcare-associated pathogens (MRSA carriage: OR, 8.0 [95% CI, 4.2-15.1]; Clostridium difficile infection: OR, 3.4 [95% CI, 2.2-5.3]; vancomycin-resistant Enterococci carriage: OR, 3.1 [95% CI, 2.5-4.0]; P < .01 for all). Select comorbidities were associated with MRSA colonization (congestive heart failure, diabetes, pulmonary disease, immunosuppression, and renal failure; P < .01 for all), while others were not (human immunodeficiency virus, cirrhosis, and malignancy). ICU admission was not associated with an increased risk of MRSA colonization (OR, 1.1 [95% CI, 0.6-1.8]; P = .87).MRSA colonization on hospital admission was associated with healthcare contact, previous healthcare-associated pathogens, and select comorbid conditions. ICU admission was not associated with MRSA colonization, although this is commonly used in state mandates for MRSA screening. Infection prevention programs utilizing targeted MRSA screening may consider our results to define patients likely to have MRSA colonization.