Colistin is increasingly used to treat infections caused by multi-drug resistant Gram-negative bacteria but colistin-resistant strains are being increasingly identified. Three extremely drug-resistant Acinetobacter baumannii (XDR) isolates (Ab3534, Ab19660 and Ab7817), which were colistin resistant, were recovered from patients. Here we characterize the drug resistance profiles and the genetic basis of colistin resistance in these isolates. Whole-genome sequence analysis indicated that all three isolates mapped as part of the mixed A. baumannii global clone GC2 and GC3 lineages. Ab3534 belonged to multi-locus sequence type ST 417, was resistant to all current antibiotics and showed extremely high colistin-resistance (MIC > 256 µg/ml). Ab19660 belonged to ST 124, was susceptible only to tigecycline with medium colistin-resistance (MIC= 64 µg/ml). Ab7817 belonged to ST 225, was susceptible to aminoglycosides and tigecycline and showed high colistin-resistance (MIC= 256 µg/ml). Although Ab3534 showed the highest colistin MIC, it reduced growth rate in colistin at concentrations > 0.5 µg/ml. Unlike Ab3534, Ab19660 and Ab7817 grew at the same rate in medium with and without colistin. Genome sequences of the isolates indicated that each contained mutations within the pmrCAB operon that have previously been associated with colistin resistance in other strains. Compared to the related colistin-sensitive A. baumannii strains ATCC 17978 and 19606, Ab3534 had 5 missense mutations within pmrCAB, of which P233S in PmrB has been previously associated with colistin resistance. Furthermore, Ab19660 had 5 mutations, of which A226V in PmrB has been associated with colistin resistance and Ab7817 had a novel pmrC1A1B allele with 89 mutations, of which S14L in PmrB has been associated with colistin resistance. This study indicates that these three clinical A. baumannii strains have likely developed colisin-resistance through mutations within the pmrABC operon that result in phosphoethanolamine addition to lipopolysaccharide. Furthermore, some colistin-resistance mutations likely impose significant fitness costs.