Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit, with substantial subsequent mortality. The mortality following VAP declined in the 1980s and 1990s. Experts suggest that little progress has been made in the outcomes from VAP since several novel interventions have failed. We nonetheless hypothesized that mortality following VAP has continued to decrease owing to advances in pulmonary critical care. We identified all adult patients with Centers for Disease Control and Prevention-defined, intensive care unit-acquired VAP between January 1, 1997, and December 31, 2008, from a prospectively collected database. A total of 793 cases of VAP occurred in the study period. Cases were divided into four periods (1997-1999, 2000-2002, 2003-2005, or 2006-2008) to compare outcomes over time. Acute Physiology and Chronic Health Evaluation II scores were stable, while mortality was significantly lower in Period 4 when compared with Periods 1 and 2 (p = 0.004 and 0.009, respectively). A logistic regression model predicting death (c statistic = 0.871) revealed age (odds ratio, 1.03; 95% confidence interval, 1.02-1.05), Acute Physiology and Chronic Health Evaluation II score (1.09, 1.05-1.14), white blood cell count (1.03, 1.00-1.06), transplant recipient (3.45, 1.40-8.53), transfusions (3.25, 1.37-7.68), and pulmonary disease (3.01, 1.67-5.45) were independent predictors of death, as was the presence of trauma (0.10, 0.06-0.18), chronic steroid therapy (0.39, 0.17-0.91), and patient length of stay (0.99, 0.98-0.99), with odds ratios less than 1.0. In addition, those patients treated in Period 1 (2.23, 1.16-4.29) or Period 2 (2.13, 1.12-4.06) had twice the risk of death following an episode of VAP when compared with those treated in the most recent period. We have shown that mortality following an episode of VAP continues to decrease over time and attribute this to advancements in pulmonary and general critical care rather than any specific interventions. Prognostic study, level II.