Objective: To investigate the prevalence and risk factors associated with multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) pneumonia among intensive care unit (ICU) patients. Methods: A total of 362 patients with pseudomonas aeruginosa pneumonia from 3 teaching hospitals ICU were enrolled in this retrospective case-control study. Patients with MDR-Pa pneumonia were assigned to MDR-Pa group (n=127), the others were assigned to non-MDR-Pa group (n=235). The prevalence of anti-pseudomonal antibiotic susceptibility was documented. Risk factors included comorbid conditions and prior healthcare exposure (hospitalizations, pseudomonas aeruginosa colonization/infection, mechanical ventilation, etc.) were detected and compared. Results: The anti-pseudomonal antibiotic susceptibility in ICU isolated strains was much lower than that of the CHINET. Multivariate logistic regression analysis showed that antibiotics treatment ≥24 h in preceding 90 days (OR =4.1, 95%CI 1.9–6.8), hospitalization ≥48 h in preceding 90 days (OR =2.8, 95%CI 1.1–5.4), residence of nursing home (OR =3.5, 95%CI 2.0–6.3), pseudomonas aeruginosa colonization or infection in preceding 1 year (OR =5.2, 95%CI 1.9–8.4) were the high risk factors for MDR-Pa pulmonary in ICU patients (P<0.05). Among the prior anti-pseudomonal antibiotic exposure, carbapenems (OR =8.3, 95%CI 3.7–22.8), fluoroquinolones (OR =6.3, 95%CI 3.2–8.2) and β-lactamase inhibitor (OR =3.2, 95%CI 1.5–6.5) were also risk factors (P<0.05). Conclusion: Patients with MDR-Pa pneumonia should be thoroughly assessed for prior healthcare exposure and anti-pseudomonal antibiotic exposure.