This study explores Taiwan high/vocational school students’ reading comprehension using different media, and further discusses functional requirements of interactive e-books, as well as the possibility of application in teaching reading comprehension. As new e-books are constantly being produced, we can learn how to design e-books suitable for teaching by first understanding students’ reading comprehension using e-books. This study designs an interactive e-book and reading comprehension scale to determine the ability of Taiwan high/vocational school students’ to read e-books. Contents of the book are related to Taiwan’s indigenous culture. Students’ reading comprehension and their ability to “access and retrieve,” “integrate and interpret” and “reflect and evaluate” when reading an interactive e-book and online e-book are observed and compared. Results show that the experimental group (interactive e-book) had better reading comprehension than the control group (online e-book), and also had better “access and retrieve” and “integrate and interpret” abilities. Indigenous students in the experimental group had significantly better reading comprehension at all levels compared with non-indigenous students. This can be interpreted as being related to contents of the e-book.