Primary care clinicians spend significant time managing nonvisit activities, including processing of requests for prescription renewal. Delays in processing refills may lead to patient dissatisfaction and impact provider productivity. Having nonclinicians process refills can be more efficient and time-saving. We aimed to evaluate the use of a multidisciplinary medication refill protocol to decrease the time to complete refill requests. We implemented nursing-driven management of refill requests within two family medicine residency clinics in Milwaukee, Wisconsin (Phase 1: single clinic implementation [March 2017-June 2019]; Phase 2: added second clinic prepandemic [June 2019-March 2020] and postpandemic [April 2020-December 2020]). The multidisciplinary refill protocol was created by faculty, residents, pharmacy, and nursing. Data were collected using electronic health record time stamps to determine when refill requests were initiated and filled by faculty, residents, and nurses. We used Mood's median test to compare the median time for medication refill completion. We used Levene's test to test for equal variance surrounding the median of each caregiver group. We used Fisher's exact test or χ2 test with Yates' correction for 2×2 contingency tables. In both phases, we identified a significant reduction in median time to refill completion ( P<.001) and variability of time to refill completion ( P<.001). Notably, in Phase 1, reduction in median refill time was most apparent among residents (383 vs 79 min postimplementation); and in Phase 2, the percentage of refills completed within 48 hours significantly increased between the pre-COVID-19 and COVID-19 pandemic among faculty and nursing in Clinic 1 and residents and faculty in Clinic 2 (all P's<.001). Implementation of a multidisciplinary refill protocol significantly improved time and predictability of refill completion in both phases.