An outbreak due to extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) was detected from May 1993 to June 1995. A total of 145 patients, particularly patients in intensive care units (ICUs) (107 patients [72%]), were colonized or infected. Infection developed in 92 (63%) patients, and primary bacteremia caused by ESBL-KP was the most frequent infection (40 of 92 patients [43%]). A single clone of ESBL-KP was identified by pulsed-field gel electrophoresis analysis throughout the whole period, and no molecular epidemiological relationship could be found between the epidemic strain and non-ESBL-KP isolates. To determine risk factors for ESBL-KP infection weekly rectal swabs were obtained in three serial incidence surveys (470 patients); the probabilities of carriage of ESBL-KP in the digestive tract were 33% (October and November 1993), 40% (May and June 1994), and 0% (October and November 1995) at 10 days of ICU admission. A logistic regression model identified prior carriage of ESBL-KP in the digestive tract (odds ratio, 3.4; 95% confidence interval 1.1 to 10.4) as an independent variable associated with ESBL-KP infection. A statistically significant correlation was observed between the restricted use of oxyimino-β-lactams (189 defined daily doses [DDD]/1,000 patient-days to 24 DDD/1,000 patient-days) and the trends of ESBL-KP infection (r = 0.7; P = 0.03).