OBJECTIVES: Previous studies have documented the impact of bacteremia involving Methicillin-resistance (MRSA) in patients with Staphylococcus aureus bacteremia, but recent estimates using nationally representative data are not available. This study compares in-hospital mortality, length of stay (LOS) and total costs between hospital discharges for MRSA and methicillin-susceptible (MSSA) S. aureus bacteremia. METHODS: Using the 2008-2009 Nationwide Inpatient Sample (NIS) data of the Healthcare Cost and Utilization Project, we developed two groups (age≥18 years): MRSA bacteremia (ICD-9-CM codes: 041.12, V09.0 and 790.7) and MSSA bacteremia (ICD-9-CM codes: 041.11 and 790.7). Given the skewed distribution of in-hospital costs and over-dispersion of LOS, generalized linear model (GLM) with gamma and negative binomial variance functions were evaluated to compare in-hospital costs and LOS, respectively, between groups. Logit model was used to compare inpatient mortality between groups. Gender, age, payer, 11 comorbidities, and hospital characteristics, including hospital location, teaching status, bed size, ownership type, and hospital region served as covariates in all regression models. RESULTS: Patients with MRSA (vs. MSSA) bacteremia were reported as a discharge diagnosis for 0.06% (vs. 0.05%) or 44,157 (vs. 37,653) of all hospital inpatient stays among adults. MRSA bacteremia inpatients had relatively longer length of hospital stay (12.5 vs. 11.1 days;P<0.01), higher total costs ($22,263 vs. $21,330;P=0.02), and increased risk of in-hospital death (2.97% vs. 2.71%;P=0.29) than inpatients with MSSA bacteremia. After adjustment for patient and hospital characteristics, MRSA bacteremia incurred 10.5% (CI:7.2-14.0%;P<0.01) longer stays, 5.6% (CI:2.0-9.4%;P<0.01) higher inpatient costs, and 0.3% (CI:17.5-22.0%;P=0.97) higher inpatient mortality than MSSA bacteremia. The annual adjusted mean incremental total inpatient cost associated with MRSA was $1,159 (SE: $379;P<0.01) per patient-discharge. CONCLUSIONS: MRSA bacteremia represents a considerable attributable burden relative to MSSA bacteremia in the US hospitals. Continued efforts towards preventing MRSA infections would provide significant potential benefits by reducing hospital resource use and costs.