Staphylococcus aureus bacteremia often persists. The reasons for persistence and its outcome are poorly defined. We conducted a prospective-observational study among 245 consecutive S. aureus (MRSA: n=125; MSSA: n=120) bacteremias (>or=1 positive blood cultures (BC)) among 234 adults (18-103-y-old; median=59 y) hospitalized during 1 January 2002-31 December 2002 at a 600-bed teaching hospital. Measurements included bacteremia duration, complication-rate (metastatic infection, relapse or attributable mortality) and outcome. Bacteremia duration was measured based on follow-up BC among 193 patients and estimated based on symptoms resolution in the rest. Measured (1-59 d; median=2) and estimated (median=1 d) duration correlated (r=0.885) though positive follow-up BC was often detected without fever (57/105 patients, 54.3%). Persistence (defined as bacteremia for >or=3 d) was noted in 84 cases (38.4%). Complication-rate increased steadily with bacteremia duration (6.6%, 24.0% and 37.7% in bacteremia for 1-2, 3 and >or=4 d, respectively; p=0.05). Cox regression analysis revealed that bacteremia duration correlated positively with endovascular sources (p=0.006), vancomycin treatment (p=0.016), cardiovascular prosthesis (p=0.025), metastatic infections (p=0.025) and diabetes (p=0.038). It is concluded that persistent bacteremia is a feature of S. aureus infection, irrespective of oxacillin susceptibility, associated with worse outcome. Risk factors include endovascular sources, cardiovascular prosthesis, metastatic infections, vancomycin treatment and diabetes. Patients at risk may benefit from novel treatment strategies.