Researchers have more often examined whether students prefer using an e-textbook over a paper textbook or whether e-textbooks provide a better resource for learning than paper textbooks, but students’ adoption of mark-up tools has remained relatively unexamined. Drawing on the concept of Innovation Diffusion Theory, we used educational data mining techniques and survival analysis to examine time to adoption of highlights, notes, annotations, bookmarks, and questions in an interactive e-textbook reader. We found that the only tool that more than half of the participants used was highlighting. Students who purchased a printed copy of the textbook had longer average times to using notes and annotations. Because most of the more interactive tools were used by a relatively small number of students, regression modeling of the factors associated with tool usage was difficult. However, there was evidence that the likelihood of using the tools decreased as the semester progressed, and that students’ self-reported reading behaviors and grade point average were predictive of the time to using the mark-up tools. An interaction between bookmark usage and amount of reading was positively associated with course grades, suggesting that a strategy of bookmarking with frequent reading could assist students to learn content successfully. The implications of this research are that (1) instructors may need to more directly scaffold the adoption of interactive e-textbook tools that are touted as boosts to student learning and (2) promoting adoption early, shortly after students begin reading the e-textbook, is critical for students to acclimate to using the tool.