OBJECTIVE To determine the attributable hospital stay and costs for nosocomial methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) primary bloodstream infections (BSIs). DESIGN Pairwise-matched (1:1) nested case-control study. SETTING University-based tertiary-care medical center. PATIENTS Patients admitted between December 1993 and March 1995 were eligible. Cases were defined as patients with a primary nosocomial S. aureus BSI; controls were selected according to a priori matching criteria. MEASUREMENTS Length of hospital stay and total and variable direct costs of hospitalization. RESULTS The median hospital stay attributable to primary nosocomial MSSA BSI was 4 days, compared with 12 days for MRSA (P=.023). Attributable median total cost for MSSA primary nosocomial BSIs was $9,661 versus $27,083 for MRSA nosocomial infections (P=.043). CONCLUSION Nosocomial primary BSI due to S. aureus significantly prolongs the hospital stay. Primary nosocomial BSIs due to MRSA result in an approximate threefold increase in direct cost, compared with those due to MSSA.