BACKGROUND AND OBJECTIVES: The frequency of multiple-antibiotic resistant bacteria has been increasing in recent years. Among the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa) shows a great propensity for the development of multidrug resistance mechanisms. The objective of this study was to identify the profile of susceptibility to antibiotics, the frequency of multidrug resistance and the cross-resistance between drugs of P. aeruginosa strains in two tertiary hospitals in Recife, Pernambuco. METHODS: The study was carried out between September 2004 and January 2006. The antimicrobial susceptibility testing was performed in 304 strains of P. aeruginosa by the disc diffusion method in accordance with National Committee for Clinical and Laboratory Standards (NCCLS) guidelines. RESULTS: The most frequent materials were urine (26.7%) and respiratory tract secretion (26.1%) The antibiotics tested and their respective susceptibilities were as follows: piperacillin-tazobactam (66.2%); aztreonam (59.8%); amikacin (59.4%); meropenem (58.2%); imipenem (57.7%); ciprofloxacin (49.7%); gentamicin and cefepime (48.6%); ceftazidime (30%) and cefotaxime (6.8%). A high prevalence of multi-resistance was detected. Half (49.7%) the strains showed resistance to three or more antibiotics and 28% were resistant to six antimicrobials or more. Also, cross-resistance between the beta-lactams (carbapenems and piperacilin/tazobactam) and aminoglicosides and quinolones was between 22.9% and 38.1%. These drugs are commonly combined in the treatment of severe infections caused by Pseudomonas, which reflects the difficulty in choosing the appropriate option for combination therapy. CONCLUSIONS: The frequency of multidrug-resistant strains of P. aeruginosa in this study was similar to other hospitals in Brazil and higher than in other countries. In order to reduce the frequency of these multiresistant clones, epidemiologic surveillance and the rational use of antibiotic protocols need to be urgently implemented.