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Summary: Background: Multidrug-resistant and extensively-drug-resistant Pseudomonas aeruginosa are increasing therapeutic challenges worldwide. We did a longitudinal epidemiological and clinical study of extensively-drug-resistant P aeruginosa in Belarus, Kazakhstan, and Russia. Methods: The study was done in three prospectively defined phases: Jan 1, 2002–Dec 31, 2004; Jan 1, 2006–Dec 31, 2007; and Jan 1, 2008–Dec 31, 2010. The first two phases were in Russia only. All consecutive, non-duplicate, nosocomial isolates and case report forms were sent to the coordinating centre (Institute of Antimicrobial Chemotherapy, Smolensk, Russia), where species reidentification, susceptibility testing, and molecular typing of isolates were done. We did susceptibility testing by agar dilution. The presence of metallo-β-lactamase (MBL) genes was established by PCR and sequencing, and class 1 integrons containing MBL gene cassettes were analysed by the PCR restriction fragment length polymorphism approach. Strain relatedness was analysed by multiple loci variable-number tandem-repeat (VNTR) analysis (at six VNTR loci) and multilocus sequence typing. Results: In 2002–04, 628 of 1053 P aeruginosa isolates were insusceptible to carbapenems and 47 (4·5%) possessed MBLs. In 2006–07, 584 of 787 isolates were insusceptible to carbapenems and 160 (20·3%) possessed MBLs. In 2008–10, 1238 of 1643 Russian P aeruginosa isolates were insusceptible to carbapenems and 471 (28·7%) possessed MBLs. Additionally, the 32 P aeruginosa isolates from Belarus and Kazakhstan were all carbapenem insusceptible and all possessed MBLs. More than 96% of MBL-positive P aeruginosa isolates were resistant to all antibiotics except colistin (ie, extensively drug resistant), and, in 2010, 5·9% were resistant to colistin. 685 (96·5%) of 710 MBL-positive P aeruginosa belonged to ST235. bla VIM-2 genes were detected in 707 (99·6%) of 710 MBL-positive isolates. Interpretation: Extensively-drug-resistant ST235 P aeruginosa has rapidly spread throughout Russia and into Belarus and Kazakhstan via clonal dissemination. Increases in the use of colistin will probably result in further spread of ST235 P aeruginosa resistant to all drugs. Funding: HEFC, Ministry of Health of the Russian Federation, Government of the Republic of Belarus, Government of the Republic of Kazakhstan, European Union, Medical Research Council UK–Canada partnership. [ABSTRACT FROM AUTHOR]