Background: Ventilator-associated pneumonia (VAP) has been reported as the most common hospital-acquired infection among patients requiring mechanical ventilation. This study aimed to determine the incidence of ventilator-associated pneumonia in a cardiopulmonary tertiary center, and to evaluate its etiology, resistance patterns, and outcome of admitted patients. Materials and Methods: In a retrospective study, patients admitted to the Masih Daneshvari Hospital, a tertiary cardiopulmonary center, were evaluated in a 7-month period. A total of 530 patients were admitted to the ICU out of which, 40 acquired VAP. Overall, 99 patients were evaluated (male= 57, female= 42) including 40 VAP and 59 non-VAP cases. The incidence of VAP was estimated to be 7.5% in this unit. The underlying conditions included respiratory diseases (COPD, asthma, etc), and cardiac problems (post "coronary artery bypass graft" CABG, etc). Also, patients in the thoracic surgery ward and those with renal, gastrointestinal, neurologic and other medical problems were evaluated. The patients were divided into two groups of VAP and non-VAP cases. The micro-organisms were recovered from the patients’ bronchoalveolar lavage fluid. Results: The most common micro-organisms recovered were Pseudomonas aeruginosa (17 cases) and Staph. aureus species (15 cases). In VAP patients in whom S. aureus was recovered, 80 percent of species were methicillin-resistant (MRSA) but all were sensitive to Vancomycin. Moreover, resistance to two, three or four antibiotics was seen in 12, 10, and 5 patients, respectively, in whom P. aeruginosa was recovered. The prevalence of S. aureus in patients with respiratory problems was more than other groups (including MRSA species). But the prevalence of recovered P. aeruginosa was the lowest in respiratory patients, compared to other groups. Also the mortality rate in drug resistant S. aureus and P. aeruginosa groups were 42 and 47 percent, respectively. Length of stay for MRSA group was 80% and death rate was 50%. In P. aeruginosa group, there was a positive relationship between resistance to multiple drugs and mortality and also ICU stay. Conclusion: VAP is a common infection in ICU setting and certain interventions may affect its incidence. In our study, P. aeruginosa and S. aureus were more common in ICU patients. Pseudomonas species were associated with the highest mortality rate and were resistant to four antibiotics in the antibiogram testing. S. aureus species were more common in patients with underlying respiratory problems, compared to those with other conditions. (Tanaffos 2010; 9(1): 21-27)