Abstract: It is often recommended that health information should be simplified for people with low health literacy. However, little is known about whether messages adapted to low health literacy audiences are also effective for people with high health literacy, or whether simple messages are counterproductive in this group. Using a two (illustrated vs. text-only) by two (nondifficult vs. difficult text) between-subjects design, we test whether older adults with low (n = 279) versus high health literacy (n = 280) respond differently to colorectal cancer screening messages. Results showed that both health literacy groups recalled information best when the text was nondifficult. Reduced text difficulty did not lead to negative attitudes or less intention to have screening among people with high health literacy. Benefits of illustrations, in terms of improved recall and attitudes, were only found in people with low health literacy who were exposed to difficult texts. This was not found for people with high health literacy. In terms of informed decisions, nondifficult and illustrated messages resulted in the best informed decisions in the low health literacy group, whereas the high health literacy group benefited from nondifficult text in general, regardless of illustrations. Our findings imply that materials adapted to lower health literacy groups can also be used for a more general audience, as they do not deter people with high health literacy.