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Off-Label Use of Multitarget Stool DNA Testing in Primary Care. INTRODUCTION: We evaluated the off-label use of multitarget stool DNA (mt-sDNA) testing in the primary care setting. METHODS: We reviewed all mt-sDNA orders between July 1, 2018, and June 30, 2019, to determine the frequency of off-label mt-sDNA orders. RESULTS: Nine hundred two patients with mt-sDNA orders were evaluated, of which 160/902 patients (17.7%) met at least 1 criterion for off-label mt-sDNA order. Increasing age was associated with off-label order (Odds Ratio [OR] 2.32 [95% CI, 1.86-2.89] for every 10-year increase in age, P < 0.0001). On multivariate analysis, increased age (OR 1.04 [1.02-1.06], P = 0.001) and need for diagnostic colonoscopy (OR 2.9 [1.01-8.34], P = 0.048) were associated with a positive mt-sDNA result. DISCUSSION: Off-label mt-sDNA testing is common, and further efforts are needed to educate patients and providers on appropriate use of mt-sDNA for colorectal cancer screening.