Background. Staphylococcus aureus bacteremia often persists and causes metastatic infections. It is unknown whether the time between blood culture incubation and growth detection (i.e., the time to positivity) in a continuously monitored system - a probable surrogate marker of bacteremia severity - correlates with outcome. Methods. We performed a prospective, observational study involving adult inpatients who had S. aureus bacteremia between 1 January 2002 and 30 June 2003 at a 600-bed teaching hospital. Measurements included time to positivity in initial blood culture series, duration of bacteremia, rate of metastatic infection, and outcome. Results. A total of 376 S. aureus bacteremias (>= 1 positive blood culture result) were reported for 357 patients aged 18 - 103 years (median age, 59 years); 64 bacteremias were excluded because blood was drawn after antibiotic therapy was started (n = 59) or through an intravascular catheter (n = 5). The source of infection was identified in 244 series (78.2%). Metastatic infection was detected in 25 bacteremias (8.0%). The mortality rate was 25.6%. The duration of bacteremia (determined in 251 series) was 1 - 59 days (median duration, 1 day; 70th percentile, 3 days). The time to positivity ranged from 4.2 to 98.2 h (median time to positivity, 15.5 h) and was significantly shorter for patients with an endovascular source of infection (14.9 +/- 5.4 vs. 19.5 +/- 10.6 P < .0005 h;), extended duration (i.e., >= 3 days) of bacteremia (14.1 +/- 4.2 vs. 18.6 +/- 9.2 h; P < .0005), and metastatic infection (12.9 +/- 5.9 vs 18.0 +/- 9.3 h; P = .007). Analysis of a range of cutoff values demonstrated that a time to positivity of <= 14 h yielded the best sensitivity and specificity for predicting the source and outcome of infection. Logistic regression analyses revealed that a time to positivity of <= 14 h was an independent predictor of an endovascular source of infection (P < .0005), extended bacteremia (P < .0005), metastatic infection (P < .0005), and attributable mortality (P = .017). Conclusions. Time to positivity in S. aureus bacteremia may provide useful diagnostic and prognostic information. Growth of S. aureus within 14 h after the initiation of incubation may identify patients with a high likelihood of endovascular infection sources, delayed clearance, and complications.