The objective of this study was to determine the effect of delayed therapy on morbidity and mortality associated with nosocomial Staphylococcus aureus bacteremia. The study included all episodes of S. aureus bacteremia that developed >2 days after hospital admission during 1999 to 2001. Classification and regression tree analysis (CART) was used to select the mortality breakpoint between early and delayed treatment. During the 25-month study period, 167 patients met the inclusion criteria. The breakpoint between delayed and early treatment derived using CART was 44.75 hours. On multivariate analysis, delayed treatment was found to be an independent predictor of infection-related mortality (odds ratio, 3.8; 95% confidence interval, 1.3-11.0; P=.01) and was associated with a longer hospital stay than was early treatment (20.2 days versus 14.3 days; P=.05). These findings support the notion that delay of therapy has deleterious effects on clinical outcomes, and efforts should be made to ensure that appropriate therapy is initiated promptly.