An observational study was undertaken to describe a nosocomial outbreak caused by multiresistant Klebsiella pneumoniae (MRKP). Ten patients in the pediatric intensive care unit (ICU) at a hospital in Madrid were colonized by or infected with MRKP from October 1997 to April 1998. Thirty-two patients with MRKP-negative surveillance cultures who were admitted to the ICU during the outbreak period were selected as control patients. Random amplified polymorphic DNA analysis of MRKP isolates revealed patterns that were indistinguishable from each other. After identification of colonized patients by surveillance cultures and implementation of standard and contact precautions, the outbreak was controlled. An age <12 weeks (odds ratio [OR], 13.1) and previous treatment with third-generation cephalosporins and aminoglycosides (OR, 31.2) were independently associated with MRKP colonization and/or infection. Individual exposure to antibiotics, irrespective of other clinical determinants, is a risk factor for MRKP acquisition. Screening high-risk patients during outbreaks and reducing the use of third-generation cephalosporins and aminoglycosides contribute to the control of these epidemics.