Purpose: American Indian adults have not experienced decreases in colorectal cancer (CRC) incidence and mortality observed in other races or ethnic groups and their screening rates are low. Decision aids that explain available CRC screening options are one potential strategy to promote screening. The goal of this study was to test the effect of a culturally adapted decision aid on CRC-related outcomes among American Indian adults, including screening-related knowledge, attitudes, self-efficacy, intentions, and screening modality preferences. Methods: We recruited American Indian adults aged 50-75 years who were not current with CRC screening. Participants viewed a 9-min multimedia decision aid that used narrative vignettes to provide educational information about screening along with messages to address culturally specific barriers and values uncovered in formative research. We conducted a single-arm (pre-post) study and assessed screening-related outcomes at baseline and immediately after viewing the decision aid. Results: Among n = 104 participants, knowledge scores increased from a mean of 36% correct to 76% correct. Participants also had statistically significant increases in positive attitudes, perceived social norms, self-efficacy, and intent. The proportion of participants who identified a preference for a specific CRC screening modality rose from 81% identified at pre-intervention to 93% post-intervention ( p = 0.013). Conclusion: Our study provides promising new findings that our culturally adapted decision aid is efficacious in educating American Indian adults about CRC screening and increases their screening intentions and ability to state modality preferences. Future research is needed to test the decision aid as a component of CRC screening interventions with American Indian adults.