To evaluate the validity and reliability of select recommended triggers, defined as flags found on review of the medical record that prompt further investigation to determine the presence or absence of an adverse drug event (ADE), selected from a list initially constructed based on severity, frequency, and detectability of triggers within a pediatric population. This was a single-center, retrospective cohort analysis of pediatric patients admitted to University of North Carolina (UNC) Children's Hospital who received trigger-associated medications between January 2015 and December 2016. Patient-care areas of the emergency department, operating rooms, and post-anesthesia care units were excluded. Trigger-detection encounters were evaluated by two reviewers using pre-established, consensus ADE criteria as determined by a panel of pediatric and medication safety specialists at UNC Medical Center. Events were categorized according to medication-related trigger and analyzed using descriptive statistics. A total of 3,836 positive triggers were included in this study. For the aggregate 12-part trigger tool package, 1,055 positive ADEs were identified, leading to a positive predictive value (PPV) of 27.5%. A 50% increase from baseline serum creatinine, resulting from co-administration of 2 or more nephrotoxic medications accounted for a total of 3,698/3,836 (96.4%). Incomplete documentation was the leading cause for event exclusion, 8/27 (30%). The triggers with the highest PPV included protamine 4/4 (100%), flumazenil 1/1 (100%), and vancomycin-related events 51/67 (76.1%), respectively. Phenytoin level >30 µg/mL or free level >2.5 µg/mL resulted in the lowest PPV, 1/12 (8.3%). This study lays the foundation for further studies to develop a robust pediatric trigger tool that may involve developing multi-element triggers, determining sensitivity and specificity of triggers, or mobilizing the trigger tool to an automated system. Trigger tools can be individualized to meet each institutions' needs and unique patient population.