Mechanical ventilation is essential for many patients with critical illness and respiratory failure, but places patients at risk of life-threatening complications termed ventilator-associated events (VAEs). VAEs occur in approximately 25% of mechanically ventilated patients. These increase duration of mechanical ventilation, intensive care unit (ICU) and hospital length of stay, healthcare costs, and risk of disability and death. Many VAEs are aspiration-associated events such as pneumonia and Acute Lung Injury (ALI); aspiration pneumonia in particular is the second most common diagnosis among hospitalized adult patients. However, the lack of standardized diagnostic methods to confirm suspicion of aspiration poses a barrier to diagnosis of aspiration-related events in mechanically ventilated patients. Therefore, development of biomarkers to detect the early occurrence of aspiration in mechanically ventilated patients is a national priority in the United States. These biomarkers would enable development of novel therapies and allow clinicians to institute such therapies early to attenuate the incidence of adverse events. Ongoing research aims to assess the sensitivity and specificity of specific biomarkers to detect occurrence of early aspiration events in adult and pediatric patients receiving mechanical ventilation. To this end, our research group is actively measuring pepsin and salivary amylase in tracheal aspirates from mechanically ventilated individuals as markers of gastric and oropharyngeal aspiration respectively. We hypothesize that aspiration events, identified by these markers, will correlate with incidence/time to VAEs and ICU outcomes including mortality, ventilator days, ICU days and hospital days. Accurate estimation of the incidence of aspiration and its impact on outcomes in mechanically ventilated patients will enable future trials of interventions to decrease morbidity/mortality from aspiration-associated pulmonary complications.