BACKGROUND Pediatric patients may be at an increased risk of adverse effects from various medications. Recently, there have been a number of serious adverse events, including several pediatric patients experiencing severe respiratory depression and death as a result of the use of codeine for pain control following tonsillectomy and adenoidectomy. OBJECTIVE To assess the safety of opioid agonists in pediatric patients undergoing operative procedures or have experienced trauma and to evaluate the risk of respiratory depression and death among this population. METHODS PubMed and Medline were searched to identify randomized controlled studies from 1994 to 2012 addressing postsurgery/trauma opioid use in pediatric patients. Relative risks and confidence intervals (CIs) were calculated using data available in clinical trials. RESULTS A total of 16 clinical trials were evaluated for this review. Randomized controlled trials included studies comparing opioids versus non-opioids for a variety of painful conditions. The relative risk of respiratory depression associated with opioid use in 1 trial was 1.63 (95% CI: 0.64-6.13). The remaining 15 trials reviewed described no significant difference in respiratory depression or adverse effects associated with treatment. No deaths were attributed to opioid use in any of these studies. CONCLUSION Opioid-associated respiratory depression was very rare and no deaths were reported in the reviewed studies. These findings under the well-defined conditions of controlled studies may not be the best means of determining overall opioid-associated side effects in pediatric patients. INDEX TERMS