Potential risk factors for the detection of imipenem-resistant Pseudomonas aeruginosa in hospitalized patients were assessed by a case-control study. Forty patients whose first P. aeruginosa isolate was resistant or intermediate to imipenem were more likely than 387 controls to have received imipenem (odds ratio [OR] = 16.9; P < .0001) and to have undergone organ transplantation (OR = 3.9; P = .008). No significant difference was found for treatments with other antibiotics, other underlying diseases, demographic characteristics, different exposures to the hospital environment, or the culture site. Imipenem-resistant P. aeruginosa isolates were more likely to be resistant to other common antipseudomonal agents than were imipenem-susceptible isolates. It is concluded that treatment with imipenem, but not with other beta-lactam drugs, is a major risk factor for the detection of imipenem-resistant P. aeruginosa in hospitalized patients, that these organisms may relatively often be resistant to other antipseudomonal agents, and that the hospital environment per se might not play a major role in their epidemiology.