Virtual simulation offers a powerful educational tool with considerable, albeit underexplored potential. This technology immerses students in lifelike digital scenarios, fostering the acquisition of knowledge and skills necessary for their future careers. This study aimed to assess knowledge acquisition and satisfaction outcomes among students using a virtual simulation teaching approach. The specific objectives were (1) to compare pre-and posttest knowledge acquisition, (2) to investigate the influence of prior professional experience on knowledge, and (3) to explore satisfaction levels with virtual simulation. One hundred and fifty-nine nursing students participated in a virtual simulation-based clinical intervention, entailing the resolution of a virtual adult patient hospitalized with respiratory pathology. Sociodemographic data and prior professional experience were collected, and knowledge was evaluated through pre-to-post tests. Satisfaction levels were assessed using open-ended questions. Quantitative data were analyzed using descriptive statistics, Wilcoxon, Mann–Whitney U, and Cohen’s tests, while qualitative data underwent keyword-in-context analysis. Significant differences were noted between pre- and posttest knowledge levels, with prior experience showing no significant impact on knowledge acquisition. Participants reported high levels of satisfaction. Lexicometric analysis identified four clusters of words related to the key terms “simulation”, “learn”, “activity”, and “knowledge”. Virtual clinical simulation effectively enhances knowledge acquisition and fosters satisfaction, with students recognizing the positive impact of this approach on their learning. Consequently, virtual simulation contributes to the training of competent health professionals.