The use of blended educational approaches, including HyFlex simulation in recent years and during the COVID-19 pandemic, has impacted medical education and has drawn attention to a new teaching method. However, integrating new teaching methods has its advantages and disadvantages. The effectiveness of HyFlex simulation is not well studied in the literature. The study aims to assess the effectiveness of HyFlex simulation-based clinical learning in comparison to traditional learning in undergraduate clinical education. The study collected demographic data, satisfaction, effectiveness, and acceptance. The data were analyzed using descriptive statistics. The mean scores of satisfactions and previous experience among graduates and students were compared using an independent sample t-test. A p-value of less than 0.05 was used as the significant level. One hundred twenty-four participants in this cross-sectional study completed an online survey. These were graduates (n = 62) and students (n = 62) from the University of Sharjah in the United Arab Emirates. The results showed that students had positive feedback about the HyFlex simulation learning method, especially the content, design, rationale, effect of simulation in acquiring knowledge and improving objective achievement. In addition, HyFlex boosted students’ knowledge enhanced student-centered learning and clinical practice assessment. However, they reported that face-to-face learning was significantly more effective for acquiring practical skills than HyFlex simulation learning.