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Introduction: In 2021, the USPSTF lowered the recommended age of colorectal cancer (CRC) screening initiation from 50 to 45 years. We assessed clinician response to the updated guideline in a major health system., Methods: This was a retrospective cohort study of average-risk, CRC screening-naïve adults aged 45-50 years with a primary care appointment between July 2018 and February 2023. We defined the pre-guideline change period as July 2018-February 2020 (pre-period) and the post-guideline change period as July 2021-February 2023 (post-period). Clinician ordering of any CRC screening type was assessed. Mixed effects Poisson regression was used to model the incidence rate ratio (IRR) of a patient receiving a screening order, including an interaction between age (45-49 years versus 50 years) and time-period (pre- versus post-guideline change.) Variation in screening orders were also described by calendar quarter and clinician., Results: There were 28,114 patients in the pre-period and 22,509 in the post-period. Compared to patients aged 40-49 years in the pre-period, those in the post-period were more likely to have screening ordered (IRR:12.1; 95%CI:11.3-13.0). The screening ordering rate increased for 50-year-olds from the pre- to the post-period (IRR:1.08;95%CI:1.01-1.16) and was slightly higher than that of 45-49-year-olds in the post-period (IRR:1.08; 95%CI:1.02-1.14). All clinicians increased their ordering rate for patients aged 45-49 years. Within five months of the guideline change, the ordering rate for 45-49-year-olds and 50-year-olds was nearly the same., Conclusions: Rapidly following the guideline change, clinicians increased their screening ordering rate for 45-49-year-olds, indicating almost complete uptake of the recommendation., Competing Interests: Declaration of competing interest No financial disclosures have been reported by the authors of this paper., (Copyright © 2024. Published by Elsevier Inc.)