Abstract According to the Institute of Medicine’s National Cancer Policy Forum, the American Cancer Society, and the National Cancer Institute, cancer screening programs are partly responsible for declining colorectal cancer (CRC) incidence and mortality rates in the U.S. Unfortunately, American Indians (AIs) have experienced either no change or an increase in CRC incidence and mortality, disproportionate diagnosis of late stage disease and poorer survival. While, nearly two-thirds of U.S. adults are current with United States Preventive Services Task Force (USPSTF) guidelines for CRC screening, AI screening rates range from only 28% to 51% in the Southwest and Southern Plains regions. One evidence-based intervention strategy for increasing CRC screening recommended by the Community Preventive Services Task Force (CPSTF) is patient navigation. By offering interpretation, transportation, social support, and culturally and linguistically appropriate education and outreach, patient navigators are able to reduce structural barriers and facilitate access to screening. While researchers have documented effectiveness of patient navigation towards enhancing cancer screening among AI populations, few studies have elucidated best practices for training patient navigators to serve in this capacity. As an effort of the AI CRC Screening Consortium formed by the National Cancer Institute-Designated Cancer Centers at the Universities of Arizona, New Mexico, and Oklahoma, we trained a cadre of 21 individuals to serve as patients navigators in six unique AI-serving health clinics and communities in Oklahoma, Arizona, and New Mexico. We used a unique blend of didactic and interactive training components (i.e. role playing, games, and group dialogues). The 2.5-day curriculum centered upon a set of nine modules that included digestive system anatomy, USPSTF CRC screening guidelines, stool-based test procedures, direct visualization test procedures, CRC risk factors, CRC diagnosis and treatment, Transtheoretical Model and Motivational Interviewing, and patient navigation tips. A 36-item pre-/post-test was administered to assess the impact of training upon navigator capacity. Paired-sample t-tests were utilized to analyze mean differences in scales measuring two key constructs – CRC-specific knowledge and self-efficacy to engage in CRC control efforts. Evaluation findings demonstrated statistically significance increases in both CRC knowledge scores (pre-test mean = 7.8/12.0 vs. post-test mean 10.9/12.0, p=0.000) and self-efficacy scores (pre-test mean = 3.8/5.0 vs. post-test mean = 4.8/5.0, p=0.001). These findings demonstrate the value of robust capacity development activities with patient navigators prior to intervention as a means of not only increase knowledge about CRC and its associated screenings, but to also engender significant readiness and confidence among patient navigators to integrate CRC control into practice. Citation Format: Kevin C English, Cheyenne Jim, Jennifer Hatcher, Mark P Doescher, Shiraz I Mishra, Peter Lance, Dorothy Rhoades, Usha Menon. Capacity development among patient navigators to enhance colorectal cancer control in American Indian-serving healthcare facilities in the U.S. Southwest and Southern Plains [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B004.