OBJECTIVES: MRSA bacteremia is associated with significantly greater mortality, length of stay (LOS), and hospital costs compared to methicillin-susceptible S. aureus (MSSA) bacteremia. With the changing epidemiology of S. aureus infections, we sought to identify risk factors for MRSA bacteremia. METHODS: Our case-control study identified MRSA (cases) or MSSA (controls) bacteremia hospitalizations, using diagnosis codes, from the 2009 Nationwide Inpatient Sample (n=7,810,762). These were further categorized into community-associated (principal diagnoses) or hospital-associated (secondary diagnoses) infections. Significant independent predictors of MRSA bacteremia, as compared to MSSA bacteremia, were identified from logistic regression models.  Differences in outcomes were assessed with χ2 or Wilcoxon tests. RESULTS: Our study included 12,907 MRSA and 9,380 with MSSA bacteremia hospitalizations. Lower median household income (<$38,999 versus $63,000 or more) was significantly associated with MRSA bacteremia (odds ratio [OR]=1.34, p<0.01). African Americans (OR=1.32, p<0.01) were at higher risk while Asian or Pacific Islanders (OR=0.80, p=0.02) were at lower risk of developing MRSA bacteremia compared to Whites. The presence of certain comorbidities increased the risk of MRSA bacteremia as compared to MSSA (p<0.01): paralysis (OR=1.65), other neurological disorders (OR=1.38), chronic pulmonary disease (OR=1.27), peripheral vascular disease (OR=1.27), psychosis (OR=1.23), weight loss (OR=1.19), and renal failure (OR=1.13). Alternatively, the odds of other comorbidities were lower with MRSA bacteremia (p<0.01): coagulopathy (OR=0.85), hypertension (OR=0.84), and metastatic cancer (OR=0.77). Similar results were found in community-associated and nosocomial infection subgroups. MRSA was associated with significantly higher mortality (MRSA 63%, MSSA 37%), LOS (MRSA 16 days, MSSA 14 days), and hospital costs (MRSA $114,176, MSSA $104,408) (p<0.01).  CONCLUSIONS: Our study identified additional predictors of MRSA bacteremia among a large, nationally representative source population of 7 million patients. These included income, race, and comorbidities, which were either risk factors for MRSA bacteremia, as compared to MSSA, or protective against MRSA, indicating a greater association with MSSA.