Understanding the risk factors for ventilator-associated pneumonia can help to assess prognosis and devise and test preventive strategies. To examine the baseline and time-dependent risk factors for ventilator-associated pneumonia and to determine the conditional probability and cumulative risk over the duration of stay in the intensive care unit. Prospective cohort study. 16 intensive care units in Canada. 1014 mechanically ventilated patients. Demographic and time-dependent variables reflecting illness severity, ventilation, nutrition, and drug exposure. Pneumonia was classified by using five methods: adjudication committee, bedside clinician's diagnosis, Centers for Disease Control and Prevention definition, Clinical Pulmonary Infection score, and positive culture from bronchoalveolar lavage or protected specimen brush. 177 of 1014 patients (17.5%) developed ventilator-associated pneumonia 9.0 +/- 5.9 days (median, 7 days [interquartile range, 5 to 10 days]) after admission to the intensive care unit. Although the cumulative risk increased over time, the daily hazard rate decreased after day 5 (3.3% at day 5, 2.3% at day 10, and 1.3% at day 15). Independent predictors of ventilator-associated pneumonia in multivariable analysis were a primary admitting diagnosis of burns (risk ratio, 5.09 [95% CI, 1.52 to 17.03]), trauma (risk ratio, 5.00 [CI, 1.91 to 13.11]), central nervous system disease (risk ratio, 3.40 [CI, 1.31 to 8.81]), respiratory disease (risk ratio, 2.79 [CI, 1.04 to 7.51]), cardiac disease (risk ratio, 2.72 [CI, 1.05 to 7.01]), mechanical ventilation in the previous 24 hours (risk ratio, 2.28 [CI, 1.11 to 4.68]), witnessed aspiration (risk ratio, 3.25 [CI, 1.62 to 6.50]), and paralytic agents (risk ratio, 1.57 [CI, 1.03 to 2.39]). Exposure to antibiotics conferred protection (risk ratio, 0.37 [CI, 0.27 to 0.51]). Independent risk factors were the same regardless of the pneumonia definition used. The daily risk for pneumonia decreases with increasing duration of stay in the intensive care unit. Witnessed aspiration and exposure to paralytic agents are potentially modifiable independent risk factors. Exposure to antibiotics was associated with low rates of early ventilator-associated pneumonia, but this effect attenuates over time.