This case study describes the challenges and solutions in implementing a randomized controlled trial to test a new educational software program for undergraduate nursing students. The software was developed through an iterative prototyping model conducted in seven stages. In the final stage, a randomized controlled trial was carried out to compare the effectiveness of the software with printed clinical cases aimed at improving students’ ability to accurately solve clinical cases. The randomized controlled trial involved 37 subjects divided into two subgroups, experimental and comparison, and two diagnostic reasoning skill measurements, before and after using the software (experimental group) or reading an instructional text (comparison group). Throughout the randomized controlled trial, we faced several challenges that were overcome by the use of creative solutions, strategic planning, and collaboration. Lessons learned from this study can be helpful for researchers who are developing a randomized controlled trial and for future research.