Most research on computerized provider order entry (CPOE) has focused on its role in preventing medication errors. This modeling study sought to determine the cost-effectiveness of CPOE in the ambulatory setting. The authors used prior data on changes in adverse drug event rates both before and after implementation of electronic prescribing to estimate the benefit of CPOE for outpatient medication safety. Exploring four simulations varying in practice sizes and characteristics, they found that CPOE was cost-effective and associated with fewer medication errors. These data support further implementation of electronic prescribing, despite concerns about introducing new errors with health information technology. A previous AHRQ WebM&M perspective discusses how to design safer CPOE systems.