The purpose of this study was to determine better strategies for the design and use of computer-assisted instruction (CAI) in health science subjects that require visual learning. Evaluation of current use of CAI was focused on three CD-based modules developed to teach histological images to beginning medical students at multiple sites. For internal control, students' learning outcomes and perceived effectiveness were analyzed with their demographic characteristics, computer attitude, computer experience, and learning behaviors being considered. Results indicated that students who used at least two different CAI programs scored significantly higher on the final examination than those who used only the CAI tool designed by their site's instructor. Further investigation indicated that students might have benefited from the interactive features of a specific CAI tool. Such scaffolds could have successfully supported encoding processes while students were restructuring their mental models. In addition, students perceived the CAI programs to be more effective when the tools were fully integrated into the curriculum. Perceived module effectiveness was significantly correlated with examination performance, suggesting a well-designed and appropriately used CAI tool may help students achieve not only learning efficiency, but also better learning outcome. Anat Rec (Part B: New Anat) 284B:28–34, 2005. © 2005 Wiley-Liss, Inc.