E-prescribing is a growing solution to prevent medication errors, with insurers rewarding the practice and high-risk settings adopting the technology. This study surveyed more than 180 ambulatory providers who use e-prescribing systems and found that respondents believed the system improved the quality of care delivered, prevented errors, and enhanced both patient satisfaction and clinical efficiency. However, less than half the respondents were satisfied with the drug interaction and allergy alerts. The authors advocate for better design of alert systems to prevent alert fatigue yet promote safe prescribing practices. The challenges of implementing effective medication decision support systems are discussed in an AHRQ WebM&M perspective.