Electronic health record (EHR) order sets are common. Order sets represent one clinical decision support (CDS) tool within computerized provider order entry systems that may promote safe, efficient, and evidence-based patient care. A small number of order sets account for the vast majority of use, suggesting that some order sets have a higher value to clinicians than others. While EHR order sets can save time and improve processes of care, it remains less clear that EHR order sets have shown definite patient outcome benefits. There are general guidelines on CDS and usability that can be applied to the development of EHR order sets. Order set success requires leadership, planning, and resources as well as ongoing maintenance and evaluation. This article describes one academic medical center’s experience in developing an EHR order set embedded with evidence-based principles and lessons learned for future order set development.