Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. This study compares the antimicrobial susceptibility of 153 P. aeruginosa isolates from the United Kingdom (UK) (n=58), Belgium (n=44), and Germany (n=51) collected from 120 patients during routine visits over the 2006-2012 period. MICs were measured by broth microdilution. Genes encoding extended spectrum β-lactamases (ESBL), metallo-β-lactamases and carbapenemases were detected by PCR. Pulsed Field Gel Electrophoresis and Multi-Locus Sequence Typing were performed on isolates resistant to ≥ 3 antibiotic classes among penicillins/cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, polymyxins. Based on EUCAST/CLSI breakpoints, susceptibility was ≤ 30%/≤ 40% (penicillins, ceftazidime, amikacin, ciprofloxacin), 44-48%/48-63% (carbapenems), 72%/72% (tobramycin), and 92%/78% (colistin) independently of patient's age. Sixty percent of strains were multidrug resistant (MDR; European Centre for Disease prevention and Control criteria). Genes encoding ESBL (most prevalent BEL, PER, GES, VEB, CTX-M, TEM, SHV, and OXA), metallo β-lactamases (VIM, IMP, NDM), or carbapenemases (OXA-48, KPC) were not detected. The Liverpool Epidemic Strain (LES) was prevalent in UK isolates only (75% of MDR isolates). Four MDR ST958 isolates were found spread over the three countries. The other MDR clones were evidenced in ≤ 3 isolates and localized in a single country. A new sequence type (ST2254) was discovered in one MDR isolate in Germany. Clonal and non-clonal isolates with different susceptibility profiles were found in 21 patients. Thus, resistance and MDR are highly prevalent in routine isolates from 3 countries, with carbapenem (meropenem), tobramycin and colistin remaining the most active drugs.