This study investigated factors affecting second/foreign language (L2) reading comprehension in a hypermedia environment within the theoretical framework of dual coding and cognitive load theories, and interactive models of L2 reading. The independent variables were reading ability, topic interest, prior topical knowledge, and the number of times participants accessed annotations. The dependent variable of interest was reading comprehension measured through a recall test. The participants were 54 senior foreign language teaching students at a state university in Turkey. The participants were given a hypertext to read for general comprehension and were told that they would be required to write down everything they remembered at the end of reading. The text was annotated with multiple forms of media: text, graphics, audio, and video. Annotations provided information both at the word level (i.e., definitions of words) and topic level (i.e., extra information about the topic). A multiple regression analysis with reading comprehension as the criterion and the independent variables mentioned above as the predictors served to reveal whether a relationship existed between the potential predictor and outcome variables. Findings indicated that topic interest and annotation look up were important variables contributing to reading comprehension in a hypermedia environment. It was also found that videos and textual information were the most useful types of annotations. It was suggested that hypermedia environments accommodated for most types of learning styles. It was also suggested that providing extra topical information through annotations compensated for the lack of prior knowledge. (Contains 3 tables.)