Bloodstream infection (BSI) due to multidrug-resistant Klebsiella is associated with high rates of morbidity and mortality. The aim of this study was to identify predictors of in-hospital mortality among patients with BSI due to ceftazidime-resistant (CAZ-R) Klebsiella pneumoniae at a tertiary care medical center. Patients with CAZ-R K. pneumoniae BSI were identified by our microbiology laboratory between January 1995 and June 2003. Clinical data were collected retrospectively. Logistic regression was used to identify independent predictors of all causes of in-hospital mortality. Of 779 patients with K. pneumoniae BSI, 60 (7.7%) had BSI due to CAZ-R K. pneumoniae; 43 (72%) of these were nosocomial infections. Pulsed-field gel electrophoresis identified a single predominant strain in 17 (28%) patients. The in-hospital mortality rate was 43% (n = 26). Among patients with CAZ-R K. pneumoniae BSI, those who died were similar to survivors with respect to demographic, clinical, and antimicrobial susceptibility characteristics. Only 43 (72%) patients received effective therapy within 5 days of BSI. In bivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was associated with death (P = 0.03). Strain genotype was not predictive of outcome. In multivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was an independent predictor of death (odds ratio, 3.32; 95% confidence interval, 1.07 to 10.3). Thus, among patients with BSI due to CAZ-R K. pneumoniae, a delay in the initiation of effective therapy of greater than 72 h after BSI was associated with a >3-fold increase in mortality risk.