While a major objective of CPOE is to reduce medication errors, its introduction is a major system change that may result in unintended outcomes. Monitoring voluntarily-reported medication errors in a university setting was used to identify the impact of initial CPOE implementation on medical-surgical and intensive care units. A retrospective trend analysis was used to compare errors one year before and six months after implementation. Total error reports increased post-CPOE but the level of patient harm related to those errors decreased. Numerous modifications were made to the system and the implementation process. The study supports the notion that CPOE configuration and implementation influences the risk of medication errors. Implementation teams should incorporate monitoring medication errors into project plans and expect to make ongoing changes to continually support the design of a safer care delivery environment.