In this 1st national surveillance study, the susceptibility pattern of 1011 consecutive isolates of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. isolated from patients hospitalized in Israel hospitals, covering 62.3% of all general hospital beds in the country, was investigated. Proportion of susceptibilities (range among institutions, MIC(50)/MIC(90) in micrograms per milliliter) were to ertapenem 95.0% (88.8-100%, 0.19/0.75), imipenem 98.8% (88.8-100%, 0.25/0.38), meropenem 98.2% (90.0-100%, 0.06/0.19), piperacillin-tazobactam 59.1% (42.6-77.0%, 16/256), ciprofloxacin 17.2% (9.0-24.6%, 32/32), levofloxacin 17.8% (9.0-24.6%, 32/32), amikacin 74.5% (63.8-98.0%, 6/32), and gentamicin 19.3% (12.3-28.5%, 96/256). Coresistance, cross-resistance, and variability between institutions were high. Only carbapenems retain predicted activity against ESBL-producing E. coli and Klebsiella spp. across Israeli hospitals.