Colorectal cancer (CRC) screening rates are suboptimal, partly due to poor communication about CRC risk. More effective methods are needed to educate patients, but little research has examined best practices for communicating CRC risk. This multi-method study tests whether tailoring CRC risk information increases screening intentions. Participants (N = 738) were randomized with a 2:2:1 allocation to tailored, targeted, and control message conditions. The primary outcome was intention to screen for CRC (yes/no). Additional variables include perceived message relevance, perceived susceptibility to CRC, and free-text comments evaluating the intervention. A chi-square test determined differences in the proportion of participants who intended to complete CRC screening by condition. A logistic-based path analysis explored mediation. Free-text comments were analyzed using advanced topic modeling analysis. CRC screening intentions were highest in the tailored intervention and significantly greater than control (P = 0.006). The tailored message condition significantly increased message relevance compared with control (P = 0.027) and targeted conditions (P = 0.002). The tailored condition also increased susceptibility (P < 0.001) compared with control, which mediated the relationship between the tailored condition and intention to screen (b = 0.04, SE = 0.02, 95% confidence interval = 0.02, 0.09). The qualitative data reflect similar trends. The theoretical mechanisms and practical implications of tailoring health education materials about CRC risk are discussed.