1607 Background: Based on the 2022 census, 20% of the U.S. population lives in rural areas. Recent literature suggests that individuals in these areas may encounter health disparities, potentially leading to higher mortality from colorectal cancer (CRC) when compared to their urban counterparts. The PREEMPT CRC is a prospective, multicenter clinical study designed to validate an investigational blood test (MyTectCRC) intended to provide a convenient and accessible option for CRC screening. PREEMPT CRC included a decentralized clinical trial (DCT) site to broaden enrollment from a wider range of geographical areas, including traditionally underrepresented rural regions. This analysis evaluates demographic characteristics of participants from rural and urban areas enrolled in two distinct strategies within the DCT sites. Methods: Eligibility criteria for PREEMPT CRC have been previously described (NCT04369053). All DCT activities occurred under one clinical study ‘Metasite’, enabled by a multichannel recruitment strategy that included 1) Direct-to-Participant (DTP) via digital enrollment and 2) Site-Based (SB) partners who supported the principal investigator by identifying participants scheduled to receive a screening colonoscopy. Participant zip codes were mapped to local counties and aligned with either 1) Metropolitan (Urban) or 2) non-Metropolitan (Rural) counties. Enrolled participants were analyzed for demographics and lifestyle behaviors such as tobacco, alcohol, and drug use. Results: The DCT site enrolled 12,137 participants, where 7,634 used DTP and 4,503 used SB. Of all DCT participants, 24.4% resided in rural areas. DTP's rural population recruitment (27.8%) was double that of the SB (13.5%). The female and male distribution was similar across the groups. A larger percentage of participants from underrepresented races overall were enrolled from urban areas; however, there were some noticeable trends in the rural population. For participants who resided in rural areas and reported their race, 12.5% of DTP participants were Black and 1.2% were Asian, compared to 9.6% and 1.2%, respectively, in SB. For participants in rural areas who reported ethnicity, within DTP, 5.1% identified as Hispanic/Latinx, compared to 14.3% Hispanic/Latinx in SB. Lifestyle behavior factors were similar between DTP and SB participants who resided in rural and urban areas. Conclusions: Through the use of a DCT, the PREEMPT CRC study reached rural areas especially through DTP methodology. Furthermore, the use of SB versus DTP showed certain shifts in demographics, these differences highlight the effectiveness of targeted outreach strategies and reflect the importance for integration of multiple methods and tools to enhance essential population characteristics across geographical locations. Clinical trial information: NCT04369053 .