The purpose of the two experiments was to investigate the potential effects of different types of visualizations and self-explanation prompts on learning human cardiovascular system in a multimedia environment. In Experiments 1 and 2, 70 and 44 college students were randomly assigned to one of the four conditions in a 2 × 2 factorial design with visualization type (animated vs. static) and prompting self-explanations (prompts vs. none) as the between subjects factors. The results of Experiment 1 revealed a positive effect of prompts on learning outcomes. Experiment 2, in which the no-prompts conditions were re-designed, partially replicated the results of Experiment 1. In addition, it revealed a significant interaction between the two factors on learning time, learning outcomes, and goal-driven self-explanations. The results of both experiments suggest that instructional designers should pay attention to learners' cognitive aspects, and utilize the combination of animated visualizations and self-explanation prompts when designing multimedia environments.