Colleges and universities have started to recognize the benefits of shifting from a professor-centered instructional paradigm that focuses on the dissemination of information to the learner to a student-centered paradigm. This latter paradigm is designed to provide an environment that enables the student to personalize, analyze, synthesize, and apply the information learned both inside and outside the classroom. Few would argue that such a paradigm shift would be best supported with the provision of a cost-effective, digitally interactive textbook that supports this type of personalized student-centered learning anywhere, anytime. Additionally, an Internet-based textbook would give the student more control of when, what, and how much he/she learns allowing for a potentially deeper exploration of content. This quantitative study was conducted to ascertain if the use of an instructionally designed, interactive college nutrition textbook (iTextbook) with embedded links to digitally-rich supporting graphics, videos, figures, and self-assessments would significantly improve students’ knowledge acquisition and application of the information as compared to the use of an identical print textbook and a static electronic textbook (eTextbook) in a Portable Digital Format (PDF). This study also looked at the time-on-task for reading the textbook content in each of the three formats. Lastly, this study assessed if students would prefer this type of instructionally designed, digitally-rich iTextbook format rather than reading the same information in a print textbook or a PDF eTextbook. The results of the study alluded that while there was a trend for a higher mean exam score measuring knowledge acquisition and application of the information read in the iTextbook group and a lower mean exam score in the eTextbook group, the scores among the three formats were not significantly different. The time-on-task spent by each group reading the textbook content was also similar among the three formats. However, the students reading the eTextbook spent a significantly longer amount of time reading the eTextbook compared to the iTextbook yet obtained the lowest average exam score among the three groups. In response to a final questionnaire, students significantly preferred the iTextbook rather than the print or eTextbook formats. College students reading a textbook in an iTextbook format obtained similar exam scores as those reading the same content in a print or eTextbook format. Compared to the iTextbook, the time-on-task was not only longer for those reading the eTextbook format but this format also produced a lower exam score measuring knowledge acquisition and application. The iTextbook format was more favorably received by college students than the print or eTextbooks formats.