Adverse drug events (ADEs) are a common source of patient harm in the ambulatory setting. A substantial proportion of ADEs are caused by preventable errors in medication prescribing or monitoring. The introduction of computerized provider order entry (CPOE) has been shown to reduce the rate of medical errors in the inpatient setting. This before–after study examined rates of ADEs in primary care practices that implemented a CPOE system in Boston and Indianapolis. At baseline, the potential ADE rate was more than seven-fold greater in Indianapolis compared to Boston. Following CPOE implementation, this rate decreased by 56% in Indianapolis but increased by 104% in Boston, and there was no change overall in preventable ADEs. A recent PSNet annual perspective reviewed the relationship and current evidence linking CPOE and patient safety.