Background: In Rwanda, nurses manage all primary care at health centres, and therefore are their clinical reasoning skills important. In this study, a web-based software that allows the creation of virtual patient cases (VP cases) has been used for studying the possibility of using VP cases for the continuous professional development of nurses in primary health care in Rwanda. Previous studies in pre-service education have linked VP cases with the enhancement of clinical reasoning, a critical competence for nurses. This study investigated the feasibility of continuous professional development through VP cases to further train in-service nurses in clinical reasoning. Method: The study used a pre-post test design. Initially, seventy-six participants completed a questionnaire as part of the pre-test phase, subsequently invited to engage with all four VP cases, and finally responded to the post-test questionnaire evaluating clinical reasoning skills. Fifty-six participants successfully completed the entire study process and were considered in the analysis. The primary outcomes of this study were evaluated using a paired t-test for the statistical analysis. Results: The results show that the mean score of clinical reasoning increased significantly from the pre-test to the post-test for all four illness areas (p < 0.001). The study findings showed no statistically significant difference in participants’ scores based on demographic factors, including whether they worked in urban or rural areas. Conclusion and recommendation: Utilizing VP cases appears to significantly enhance the continuous professional development of nurses, fostering a deliberate learning process that enables them to reflect on how they manage cases and, in turn, refine their clinical reasoning skills. This study strongly recommends incorporating VP cases in the continuous professional development of nurses at the primary health level (health centers). This is especially pertinent in a context where nurses are required to perform diagnostic processes similar to those employed by physicians. © The Author(s) 2024.