The purpose of the study was to assess the effectiveness of supplementing traditional classroom teaching with Web-based learning design when teaching intramuscular injection nursing skills. Four clusters of nursing students at a junior college in eastern Taiwan were randomly assigned to experimental and control groups. A total of 147 students (80 in the experimental group, 67 in the control group) completed the study. All participants received the same classroom lectures and skill demonstration. The experimental group interacted using a Web-based course and were able to view the content on demand. The students and instructor interacted via a chatroom, the bulletin board, and e-mail. Participants in the experimental group had significantly higher scores on both intramuscular injection knowledge and skill learning. A Web-based design can be an effective supplementing learning tool for teaching nursing knowledge and skills.