Methicillin-resistant Staphylococcus aureus (MRSA) is a common and important cause of colonization and infection in medical intensive care units (ICU). The aim of this study was to assess association factors between MRSA nasal colonization and subsequent infections in medical ICU patients by clinical investigation and molecular genotyping. A prospective cohort observational analysis of consecutive patients admitted to medical ICUs between November 2008 and May 2010 at a tertiary teaching hospital were included. To detect MRSA colonization, the specimens from the nares were obtained within 3 days of admission to the ICU and again 1 week following admission to the ICU. Genetic relatedness for colonized and clinical isolates from each study patient with MRSA infection were analyzed and compared. A total of 1266 patients were enrolled after excluding 195 patients with already present MRSA infections. Subsequent MRSA infection rates were higher in patients with nasal colonization than in those without (39.1% versus 14.7%, respectively). Multivariate Poisson regression analysis demonstrated that nasal MRSA colonization (relative risk [RR]: 2.50; 95% confidence interval [CI]: 1.90-3.27; P < 0.001) was independent predictors for subsequent MRSA infections. History of tracheostomy, however, was a protective predictor in all patients (RR: 0.38; 95% CI: 0.18-0.79; P = 0.010) and in patients with MRSA nasal colonization (RR: 0.22; 95% CI: 0.55-0.91; P = 0.037). Molecular genetics studies revealed that most MRSA isolates were healthcare-associated clones and that nasal and clinical isolates exhibited up to 75% shared identity. Methicillin-resistant S. aureus nasal colonization was significantly associated with subsequent MRSA infection among medical ICU patients. Previous MRSA infection was associated with subsequent MRSA infections, and history of tracheostomy associated with reducing this risk. Most MRSA isolates were healthcare-associated strains that were significantly correlated between nasal and clinical isolates.