27 Background: Colorectal cancer (CRC) is the second most deadly and fourth most frequently diagnosed cancer in the United States. Early detection can improve CRC outcomes, but overall screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test, which includes patient and provider navigation support. Cross-sectional adherence with the mt-sDNA test was previously reported in a large Medicare population (71%). In the current study we investigated cross-sectional adherence with the mt-sDNA test in a broader, national sample of insured patients. Methods: Aggregate data from Exact Sciences Laboratories LLC (ESL; Madison, WI) were retrospectively analyzed in compliance with HIPAA requirements. Study participants included individuals ages 50 years and older who were covered by commercial insurance or Medicare, had a valid mt-sDNA test order placed between January 1–December 31, 2018, and received a test kit shipped from ESL. Cross-sectional adherence, defined as successful completion and return of the test kit within 365 days of the shipment date, was assessed overall and by patient- and provider-level factors. Results: In total, 1,420,460 participants met the study criteria (61.2% women; mean age 65.7 years). Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance (p<0.001). Adherence increased by participant age (p<0.001): 60.8% for ages 50-64, 71.3% for ages 65-75, and 74.7% for ages 76+ years. For Traditional Medicare patients, ages 65-75, adherence was 73.6%. Participants with mt-sDNA tests ordered placed by gastroenterologists had a higher adherence rate (78.3%) than those with orders placed by primary care clinicians (67.2%) (p<0.001). Adherence rates were highest among patients with ordering providers in the Pacific region (71.4%) and West North Central region (70.1%), and lowest in the Mid-Atlantic region (65.7%), New England (65.2%), West South Central region (64.6%), and Puerto Rico and US territories (60.7%). Conclusions: Novel data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test (66.8%), supporting the substantial contribution this guideline-endorsed option plays in average-risk CRC screening. At the patient-level, adherence increased with patient age, and was highest in those covered by Traditional Medicare. Provider-level stratification showed the highest adherence for mt-sDNA tests ordered by gastroenterologists. This study adds to data regarding the impact of accompanying navigation support and at-home convenience of mt-sDNA on screening completion rates.