Background: A computer simulation-based communication education program with interactive and individualized learning features for nursing students is greatly needed. The specific objectives of this study were to develop a computer simulation-based, interactive, communication education (ComEd) program, and to assess the feasibility, acceptability, and effectiveness of the program regarding nursing students' communication knowledge, learning self-efficacy, communication efficacy, and learning satisfaction. Methods: This study used the ADDIE model (Analysis, Design, Development, Implementation, and Evaluation) for the systematic development of the program. A one-group pretest-posttest quasiexperimental design was conducted with 30 nursing students to assess its feasibility, acceptance, and effectiveness. Results: All participants completed the program without difficulties and expressed satisfaction with this new method of communication education. Additionally, the program improved participants' communication knowledge, learning self-efficacy, and communication efficacy. Conclusion: Repetitive learning through the ComEd program was shown to improve nursing students' therapeutic communication skills.