This study assesses the impact of computerized physician order entry (CPOE) implementation in pediatric hospitals on reported adverse drug events. Using a nested matched case-control design; we linked CPOE implementation information from the health information management systems society analytics database with reported adverse drug event (ADE) from the national association of children's hospitals and related institutions case mix comparative data program. Differences were examined using univariate and multivariate conditional logistic regression analyses. Patients from CPOE hospitals were more frequently seen in larger hospitals have more co-morbidities than those from non-CPOE hospitals. When matched by admitting diagnosis, age, gender and race, ADE cases were associated with more reported co-morbidities, and were reported less frequently in hospitals with CPOE. Patients from hospitals without CPOE were 42% more likely to experience reportable ADE after adjusting for the presence of co-morbidities. In conclusion, we found significant beneficial associations between reportable ADE and CPOE adoption in a representative sample of pediatric hospitals. Copyright © 2009 John Wiley & Sons, Ltd.