BACKGROUND: The Tigecycline Evaluation and Surveillance Trial is an antimicrobial susceptibility surveillance program that collects gram-positive and gram-negative organisms globally. OBJECTIVE: This analysis reports on antimicrobial susceptibility among 23,918 gram-negative isolates collected from intensive care units globally between 2004 and 2009. METHODS: MICs and susceptibility were determined according to the guidelines of the Clinical and Laboratory Standards Institute (US Food and Drug Administration breakpoints were applied against tigecycline). RESULTS: Gram-negative isolates were collected from 6 geographical regions: North America, 8099 isolates; Europe, 9244; Asia-Pacific Rim, 1573; Latin America, 3996; the Middle East, 635; and Africa, 371. North America reported the lowest rates of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli both overall (12.8% and 4.7%, respectively) and in each year of collection. High rates of ESBL production were reported among K pneumoniae from Latin America (45.5%) and Africa (54.9%) and for E coli from the Middle East (32.4%). Imipenem and tigecycline maintained >90% susceptibility against K pneumoniae, E coli, Klebsiella oxytoca, Enterobacter cloacae, and Serratia marcescens for all regions. Susceptibility to meropenem was >90% against all K oxytoca and S marcescens. Large regional variations in susceptibility among Acinetobacter baumannii were reported, with the largest variations reported for amikacin (75.2% in North America, 21.8% in the Middle East) and meropenem (60.4% in North America, 15.9% in Africa). MIC(90) values for tigecycline against A baumannii were low (1-2 mg/L) for all regions. Against P aeruginosa, susceptibility to amikacin (97.5% in North America, 67.5% in Latin America) and meropenem (79.1% in North America, 51.4% in Africa) had the largest variations. CONCLUSIONS: Antimicrobial resistance among gram-negative intensive care unit isolates was highly variable between geographic regions. The carbapenems were active in vitro against Enterobacteriaceae, A baumannii and P aeruginosa, and tigecycline continued to be active in vitro against members of the Enterobacteriaceae and A baumannii collected from intensive care units in North America, Europe, the Asia-Pacific Rim, Latin America, the Middle East, and Africa.