Instructional videos have been widely used in online learning environments. Effective video learning requires self-regulation by learners, which can be facilitated by deliberate instructional design, such as through prompting. Grounded in the interactive, constructive, active, and passive (ICAP) framework, this study compared the effects of explanation prompts and explored how they affected the retention and transfer of learning. In an online experiment, 103 participants were randomly assigned to focused self-explanation, scaffolded self-explanation, and instructional explanation prompting conditions. The results indicated better retention performance from the scaffolded prompt than from the focused prompt. No differences were found in transfer performance across various forms of prompts. Regression analysis suggested that prior knowledge and cognitive load may have interacted with the effect of self-explanation prompts. Prior knowledge positively predicted transfer performance, and cognitive load negatively predicted transfer performance when focused or scaffolded prompts were implemented. Potential explanations concerning how self-explanation prompts affect learning were discussed.