Introduction: Nosocomial pneumonia (NP) and ventilator associated pneumonia (VAP) occur most frequently in intensive care units (ICU). This study seeks to determine the etiological agents of NP and VAP along with their antibacterial susceptibility patterns, and to evaluate the factors contributing to patient mortality. The impact of appropriate therapy in terms of three parameters (body temperature, PaO2/FiO2 ratio and leukocyte count) was also assessed. Methodology: This study involved 836 adult patients admitted to ICUs at the Nemazee Hospital, Shiraz, Iran, over nine months during 2008 and 2009. The inclusion criterion was the commencement of infection at least 48 hours following hospital admission. Clinical parameters including core temperature, leukocyte count. and PaO2/FiO2 ratio were evaluated. Antibiotic sensitivities of the isolated bacteria to a panel of antibiotics were determined using E-test. Results: Of 836 cases, only 58 (6.9 %) cases of NP were diagnosed, of which 42 (72 %) were VAP. A. baumannii, MRSA, P. aeruginosa and MSSA were the most prevalent bacteria. Significant correlations between previous antibiotic therapy (p = 0.04), use of corticosteroids (p = 0.02) and attributable mortality were found. A strong correlation between fever abatement and the ratio of PaO2/FiO2 with responses to treatment and outcomes was also evident. Conclusions: Combined treatment with meropenem/imipenem, ciprofloxacin and vancomycin seems to be appropriate and could cover all possible infective agents. To reduce mortality rate, reasonable prescription of antibiotics and corticosteroids could be effective. Furthermore, adopting a strategy to reduce body temperature and PaO2/FiO2 ratio could be beneficial in patients' outcomes.