Risk factors for acquisition of imipenem-resistant Pseudomonas aeruginosa by hospitalized patients were assessed at a tertiary care hospital. Two case-control studies with different control groups were used. In Study 1, patients with imipenem-resistant P. aeruginosa (IRPA) (case group) were compared with patients selected at random from the same unit. In Study 2, the case group was compared with patients with imipenem-susceptible P. aeruginosa (ISPA). Ninety-three patients with IRPA and 93 control patients were included in Study 1, and 93 IRPA patients and 65 patients with ISPA were included in Study 2. Carbapenem treatment [odds ratio (OR) 5.82], mechanical ventilation (OR 3.22) and hospital admission in the previous year (OR 2.59) were associated with IRPA in Study 1. An interaction between carbapenem and vancomycin was found to be a significant risk factor for IRPA (OR for carbapenem in patients with vancomycin use 43.71). In Study 2, carbapenem exposure (OR 12.82) and renal failure (OR 5.00) were associated with IRPA. Our study confirmed that carbapenem exposure is the main risk factor for IRPA, and found that the use of both carbapenem and vancomycin can increase this effect.