Prescribing errors represent a safety risk for hospitalized patients, especially in pediatrics. Computerized physician order entry (CPOE) might reduce prescribing errors, although its effect has not yet been thoroughly studied on pediatric general wards. This study investigated the impact of a CPOE on prescribing errors in children on general wards at the University Children’s Hospital Zurich. We performed medication reviews on a total of 1000 patients before and after the implementation of a CPOE. The CPOE included limited clinical decision support (CDS) such as drug-drug interaction check and checks for duplicates. Prescribing errors, their type according to the PCNE classification, their severity (adapted NCC MERP index), as well as the interrater reliability (Cohen’s kappa), were analyzed. Potentially harmful errors were significantly reduced from 18 errors/100 prescriptions (95% CI: 17–20) to 11 errors/100 prescriptions (95% CI: 9–12) after CPOE implementation. A large number of errors with low potential for harm (e.g., “missing information”) was reduced after the introduction of the CPOE, and consequently, the overall severity of potential harm increased post-CPOE. Despite general error rate reduction, medication reconciliation problems (PCNE error 8), such as drugs prescribed on paper as well as electronically, significantly increased after the introduction of the CPOE. The most common pediatric prescribing errors, the dosing errors (PCNE errors 3), were not altered on a statistically significant level after the introduction of the CPOE. Interrater reliability showed moderate agreement (Κ= 0.48).Conclusion: Patient safety increased by reducing the rate of prescribing errors after CPOE implementation. The reason for the observed increase in medication reconciliation problems might be the hybrid system with remaining paper prescriptions for special medication. The lacking effect on dosing errors could be explained by the fact that a web application CDS covering dosing recommendations (PEDeDose) was already in use before the implementation of the CPOE. Further investigations should focus on eliminating hybrid systems, interventions to increase the usability of the CPOE, and full integration of CDS tools such as automated dose checks into the CPOE.What is Known:•Prescribing errors, especially dosing errors, are a common safety threat for pediatric inpatients.•The introduction of a CPOE may reduce prescribing errors, though pediatric general wards are poorly studied.What is New:•To our knowledge, this is the first study on prescribing errors in pediatric general wards in Switzerland investigating the impact of a CPOE.•We found that the overall error rate was significantly reduced after the implementation of the CPOE. The severity of potential harm was higher in the post-CPOE period, which implies that low-severity errors were substantially reduced after CPOE implementation. Dosing errors were not reduced, but missing information errors and drug selection errors were reduced. On the other hand, medication reconciliation problems increased.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-023-04894-5.