This study investigates the effects of topic interest and prior knowledge on text recall and annotation use of second language learners engaged in reading a hypermedia text. The participants were proficient learners of English enrolled in an undergraduate English Language Teaching programme. They were asked to read a hypermedia text that incorporated word-level and topic-level annotations, and complete an immediate recall task. Participants’ interaction with the text was recorded during the reading task. Data collection tools also included a topic interest questionnaire, a prior knowledge test, and semi-structured interviews. Results indicated no meaningful relationship between topic interest and prior knowledge. Moreover, topic interest had a significant main effect on text recall while prior knowledge did not. In other words, topic interest facilitated the number of propositions recalled. Finally, a significant interaction between topic interest and prior knowledge was found in terms of access to annotations. When topic interest was low, the participants with low prior knowledge utilized content-related annotations more frequently than those with high prior knowledge. On the other hand, when topic interest was high, the participants with high prior knowledge accessed content-related annotations more frequently than those with low prior knowledge.