We conducted a retrospective cohort study in the medical intensive care unit of Chaing Mai University Hospital to describe the epidemiology of ventilator-associated pneumonia (VAP) and identify prognostic indicators of 30-day VAP mortality. A total of 621 patients diagnosed with VAP between January 2005 and December 2011 were included. The overall 30-day mortality rate was 44.4%. The major causative pathogens were Acinetobacter baumannii (54.3%), Pseudomonas aeruginosa (35.2%), and methicillin-resistant Staphylococcus aureus (15.1%). Most A. baumannii (90.2%) comprised drug-resistant strains. Identified prognostic indicators were co-morbid malignancy (hazard ratio [HR] = 1.60; 95% confidence interval [CI] 1.02–2.42; P = 0.040), septic shock (HR = 2.51; 95% CI, 1.60–4.00; P < 0.001), Simplified Acute Physiology Score II >45 (HR = 1.62; 95% CI, 1.03–2.56; P = 0.041), Sequential Organ Failure Assessment score >5 (HR = 3.40; 95% CI 2.00–5.81; P < 0.001), and delayed inappropriate empirical antibiotic treatment (HR = 2.23; 95% CI, 1.12–4.45; P = 0.022). VAP was associated with high mortality. The major causative pathogen was drug-resistant A. baumannii. Therefore, early detection of VAP by surveillance in mechanically ventilated patients leading to earlier treatment may improve patient outcomes. Guidelines for prescribing appropriate empirical antibiotics to cover drug-resistant bacteria could be established using local epidemiological data.