Previous research has found that CancelRx can improve communication between electronic health record (EHR) systems and pharmacy dispensing systems and increase successful medication discontinuation. This interrupted time series analysis assessed the impact of CancelRx implementation on successful discontinuation of medications e-prescribed in ambulatory healthcare settings. After CancelRx implementation, the proportion of e-prescriptions sold after discontinuation in the EHR decreased from 8.0% to 1.4%.