BackgroundDirect oral anticoagulant medications are commonly used to treat or prevent thrombotic conditions, such as pulmonary embolism, deep vein thrombosis, and atrial fibrillation. However, up to 10–15% of patients receiving these medications get unsafe doses based on a patient’s kidney or liver function, potential interactions with other medications, and indication for taking the medication. Alert systems may be beneficial for improving evidence-based prescribing, but can be burdensome and are not currently able to provide monitoring after the initial prescription is written.Methods/designThis study will improve upon existing alert systems by testing novel medication alerts that encourage collaboration between prescribers (e.g., physicians, nurse practitioners, physician assistants) and expert pharmacists working in anticoagulation clinics. The study will also improve upon the existing alert system by incorporating dynamic long-term monitoring of patient needs and encouraging collaboration between prescribers and expert pharmacists working in anticoagulation clinics. Incorporating state-of-the-art user-centered design principles, prescribing healthcare providers will be randomized to different types of electronic health record medication alerts when a patient has an unsafe anticoagulant prescription. We will identify which alerts are most effective at encouraging evidence-based prescribing and will test moderators to tailor alert delivery to when it is most beneficial. The aims of the project are to (1) determine the effect of notifications targeting existing inappropriate DOAC prescriptions; (2) examine the effect of alerts on newly prescribed inappropriate DOACs; and (3) examine changes in the magnitude of effects over time for both the new prescription alerts and existing prescription notifications for inappropriate DOACs over the 18-month study period.DiscussionFindings from this project will establish a framework for implementing prescriber-pharmacist collaboration for high-risk medications, including anticoagulants. If effectively implemented at the more than 3000 anticoagulation clinics that exist nationally, hundreds of thousands of patients taking direct oral anticoagulants stand to benefit from safer, evidence-based healthcare.Trials registrationNCT05351749.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13012-023-01273-4.