Background Clinical trials exploring optimal sedation management in critically ill pediatric patients are urgently needed to improve both short- and long-term outcomes. Concise operational definitions that define and provide best-available estimates of sedation-related adverse events (AE) in the pediatric population are fundamental to this line of inquiry. Objectives To perform a multiphase systematic review of the literature to identify, define, and provide estimates of sedation-related AEs in the pediatric ICU setting for use in a multicenter clinical trial. Methods In Phase One, we identified and operationally defined the AE. OVID-MEDLINE and CINAHL databases were searched from January 1998 to January 2012. Key terms included sedation, intensive and critical care. We limited our search to data-based clinical trials from neonatal to adult age. In Phase Two, we replicated the search strategy for all AEs and identified pediatric-specific AE rates. Results We reviewed 20 articles identifying sedation-related adverse events and 64 articles on the pediatric-specific sedation-related AE. A total of eleven sedation-related AEs were identified, operationally defined and estimated pediatric event rates were derived. AEs included: inadequate sedation management, inadequate pain management, clinically significant iatrogenic withdrawal, unplanned endotracheal tube extubation, post-extubation stridor with chest-wall retractions at rest, extubation failure, unplanned removal of invasive tubes, ventilator-associated pneumonia, catheter-associated bloodstream infection, Stage II+ pressure ulcers and new tracheostomy. Conclusions Concise operational definitions that defined and provided best-available event rates of sedation-related AEs in the pediatric population are presented. Uniform reporting of adverse events will improve subject and patient safety.