Abstract Colorectal cancer (CRC) is one of the leading causes of cancer mortality in the US. While there have been significant advances in CRC screening technology over the past decades, and despite the known survival benefits when cancer is detected early, low CRC screening rates persist among minority and underserved populations(1,2) . African Americans have the highest CRC incidence and mortality of any racial/ethnic group in the United States (1,3,4). The American Cancer Society (1) reports that African Americans have a 20% higher incidence rate and a 45% higher mortality rate than non-Hispanic whites. In fact, although CRC mortality has declined by 39% among non-Hispanic whites since 1960, mortality among African Americans has increased by 28% (5). Higher mortality rates among African Americans may be largely explained by the later stage at which CRC is diagnosed (6) emphasizing the importance of improving adherence to screening guidelines in this population. Furthermore, CRC screening rates among African Americans, at 55.5%, are significantly lower than rates among whites (61.5%)(7) Relatedly, Latinos are the largest and fastest growing immigrant population in the U.S.(8) . Although Latinos have lower CRC incidence and mortality rates than whites, CRC still looms as the second most common malignancy, and the second and third leading cause of cancer death among Latino males and females, respectively (7,9). They also have some of the lowest screening rates of all ethnic groups. For example, as of 2010, the completion rate for either the fecal occult blood test (FOBT) or endoscopy among individuals eligible for screening only 47.0% for Latinos(7). Patient navigation (PN; (10) involving a specifically trained person within the health care setting who helps the patient to obtain medical care has received considerable attention as a way to improve participation in cancer screening among minority patients. Most published PN programs assist patients in obtaining follow-up of suspicious findings and cancer treatment. Several studies and national programs have reported that PN for individuals with abnormal findings or cancer diagnoses is beneficial and potentially life-saving. More recently, PN has been expanded to assist with obtaining cancer screening. Studies, mainly focused on breast and cervical screening, report that PN increases screening adherence, see review (11). Recent studies, such as Lasser, et al. and Percac-Lima et al. (12,13) showed significant differences for colonoscopy completion between navigated and non-navigated groups; however completion rates for both groups were still below 40%. Our group was among the first to introduce PN to facilitate completion of colonoscopy among minority primary care patients, which resulted in an improved adherence rate initially from 40% to 66% of all patients over a three-year period (14). As we have examined different methods of PN (i.e., peers, in conjunction with print materials) and with Direct Access Colonoscopy (DAC) we have seen completion rates increase to between 75% and 80%. By avoiding a pre-procedure visit to the endoscopist, DAC reduces wait time before a colonoscopy and decreases the need for multiple clinic visits (15,16). Over the last fifteen years, the DAC referral system has become increasingly incorporated into standard clinical practice in the United States (17). The New York Citywide Colon Cancer Control Coalition (C5) and the New York City Department of Health and Mental Hygiene (NYCDOHMH) developed a Direct Referral Initiative for screening colonoscopies (15). Likewise, we have been using a DAC system at our institution since 2003(14). This presentation will present the findings from four consecutive studies of PN. In the first, as part of a NCI R01 RCT, we examined the potential advantage of peers as navigators, compared with professional navigators in a low income African American population. Overall, the adherence rate was 76.0% among those navigated (411 randomized). Given the successful training and use of Peer Navigators, we explored the potential of this model in non-Academic sites via an NCI R25 grant, also with African Americans. Here we found a slightly lower adherence rate, 66% (206 randomized), but had many challenges in a non-Academic site which will be discussed. The third study looked at standard PN compared with enhanced PN, targeting the messaging for low income Latinos. Here we were able to randomize 461 people, with a colonoscopy completion rate of 81.1% Finally, in the fourth study, funded by NCI, we examined the potential advantage of adding print materials (both standard and culturally targeted) to PN for low-income Latinos. The colonoscopy completion rate was similar to the other study with Latinos, at 80.1%, with 386 people randomized. We will present data on the success of each program, along with the costs of implementation and overall challenges as well as challenges to dissemination.