The rate of ceftazidime resistance among Klebsiella pneumoniae isolates recovered from patients at the Cleveland Department of Veterans Affairs Medical Center increased from 6% in the first quarter of 1993 to 28% in the first quarter of 1994. The outbreak was hospitalwide, with the highest rates of resistance occurring on wards where ceftazidime was administered most frequently. Although many plasmid patterns were observed in the clinical isolates, molecular epidemiological analysis with use of pulsed field gel electrophoresis revealed substantial similarities between the strains; this finding suggested that most of the strains—if not all of them—were derived from the original clone. The addition of piperacillin/tazobactam to the hospital formulary and educational efforts focused on minimizing the administration of ceftazidime were associated with a marked decrease in the drug's use and a concomitant decrease in the percentage of ceftazidime-resistant isolates. We have not yet observeda significant rise in the rate of resistance to piperacillin/tazobactam among clinical isolates of K. pneumoniae.