Multidrug-resistant (MDR) Pseudomonas aeruginosa isolates are increasing worldwide and greatly limit therapeutic options, particularly when considering extensively drug-resistant (XDR) or pandrug-resistant isolates. The resistance profile of P. aeruginosa isolates from a Portuguese central hospital was surveyed during 10 years (n=3,778). About 39.9% were classified as MDR and 2.9% as XDR. Statistical analysis (Mann-Whitney test and regression modeling) revealed a decrease in total MDR rates over time but an increase in XDR rates. This suggests a tendency for higher proportions of XDR isolates in the future, which is of great concern. Isolates of nosocomial origin presented similar results to total population but, when analyzing them according to the different wards of origin, it was still observed a trend of increase in MDR rates in some wards, particularly pneumology, neurology, and neurosurgery. Similar analysis considering the nosocomial specimen source revealed a negative trend of evolution in MDR rates of respiratory origin and a positive trend over time in XDR rates of isolates collected from urine. Regarding the association of antibiotic resistance to MDR and XDR profiles, it was observed a negative relation over time between imipenem resistance and MDR and gentamicin resistance and XDR, suggesting that resistance to these antibiotics may predict the absence of MDR or XDR in P. aeruginosa isolates, respectively. Similar studies in other European hospitals should be performed to give further information to physicians, important for their empirical antibiotherapy regimens.