Several studies have suggested that resistance determinants usually reduce virulence. However, their contribution to decrease bloodstream infections is unclear. Our aim was to identify risk factors of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) bacteremia and to assess the prevalence of XDR-PA bacteremia. A retrospective study of PA bloodstream infections in our patient population with at least one clinical sample isolate due to PA (2006-2007) was carried out. A total of 2,131 patients with PA clinical samples were detected. Among 1,657 patients with susceptible-PA isolates, 95 developed PA-susceptible bacteremia. Concomitantly, among 474 patients with multidrug-resistant (MDR)-PA isolates, 265 with XDR-PA, and 209 with non-XDR MDR-PA, 43 developed XDR-PA bacteremia and 13 non-XDR MDR-PA bacteremia, respectively. Pulsed-field gel electrophoresis (PFGE) revealed the clonal nature of the two predominant XDR-PA phenotypes and genetic heterogeneity in non-XDR MDR-PA phenotypes. The proportion of XDR-PA bacteremia was higher than the proportion of bacteremia in the susceptible-PA population (16 % vs. 6 %; p < 0.001). A logistic regression model identified prior exposure to fluoroquinolones [odds ratio (OR) 2.80; 95 % confidence interval (CI) 1.02 to 7.70] as the independent variable associated with XDR-PA bacteremia. Our study suggests that XDR-PA strains have a greater ability to develop bacteremia. It remains unclear as to whether this invasive capacity depends on clonal traits or on other virulence determinants.