BACKGROUND: The transformation of healthcare during COVID-19 with the rapid expansion of telemedicine visits presents new challenges to chronic care and preventive health providers. Clinical decision support (CDS) is critically important to chronic care providers, and CDS malfunction is common during times of change. It is essential to regularly re-assess an organization's ambulatory CDS program to maintain care quality. This is especially true after an immense change, like the COVID-19 telemedicine expansion. OBJECTIVE: Our objective is to re-assess the ambulatory CDS program at a large academic medical center in light of telemedicine's expansion in response to COVID-19. METHODS: Our clinical informatics team devised a practical framework for an intra-pandemic ambulatory CDS assessment focused on the impact of the telemedicine expansion. This assessment began with a quantitative analysis comparing CDS alert performance in the context of in-person and telemedicine visits. Board-certified physician informaticists then completed a formal workflow review of alerts with inferior performance in telemedicine visits. Informaticists then reported on themes and optimization opportunities through the existing CDS governance structure. RESULTS: Our assessment revealed that 10 of our top 40 alerts by volume were not firing as expected in telemedicine visits. In 3 out of the top 5 alerts, providers were significantly less likely to take action in telemedicine when compared to office visits. Cumulatively, alerts in telemedicine encounters had an action taken rate of 5.3% (3,257/64,938) compared to 8.3% (19,427/233,636) for office visits. Observations from a clinical informaticist workflow review included: (1) Telemedicine visits have different workflows than office visits. Some alerts developed for the office were not appearing at the optimal time in the telemedicine workflow. (2) Missing clinical data is a common reason for decreased alert firing seen in telemedicine visits. (3) Remote patient monitoring and patient-reported clinical data entered through the portal could replace data collection usually completed in the office by an MA or RN. CONCLUSIONS: In a large academic medical center at the pandemic epicenter, an intra-pandemic ambulatory CDS assessment revealed clinically significant CDS malfunctions that highlight the importance of re-assessing ambulatory CDS performance after the telemedicine expansion.