Initial antibiotic therapy is an important determinant of clinical outcomes in ventilator-associated pneumonia (VAP). Several studies have investigated this issue, with conflicting results. This study investigated risk factors of inadequate empirical antimicrobial therapy and its impact on outcomes for patients with a clinical diagnosis of VAP. The primary outcome was adequacy of antimicrobial therapy. Secondary outcomes were duration of mechanical ventilation, hospital and intensive care unit (ICU) lengths of stay, and mortality due to VAP. Mean age was 62.9+/-15.2 years, mean APACHE (Acute Physiological Assessment and Chronic Health Evaluation) II score was 20.1+/-8.1 and mean MODS (Multiple Organ Dysfunction Score) was 3.7+/-2.5. Sixty-nine (45.7%) of 151 patients with a clinical diagnosis of VAP received inadequate antimicrobial treatment for VAP initially. There were 100 (66.2%) episodes of VAP caused by multidrug-resistant pathogens, of which 56% were inadequately treated, whereas the rate of inadequate antimicrobial therapy for VAP caused by susceptible-drug pathogens was 25.5% (P<0.001). Multiple logistic regression analysis revealed that the risk of inadequate antimicrobial treatment was more than twice as great for patients with late-onset VAP [odds ratio (OR), 2.93; 95% confidence interval (CI), 1.30-6.64; P=0.01], and more than three times for patients with VAP caused by multidrug-resistant pathogens (OR, 3.07; 95% CI, 1.29-7.30; P=0.01) or with polymicrobial VAP (OR, 3.67; 95% CI, 1.21-11.12; P=0.02). Inadequate antimicrobial treatment was associated with higher mortality for patients with VAP. Two of three independent risk factors for treatment inadequacy were associated with the isolation and identification of micro-organisms.