This paper describes a next-generation nursing education simulator, the endotracheal suctioning training environment simulator (ESTE-SIM), which is capable of interactively reproducing vital reactions. With the spread of home treatment, care providers who have received a certain level of nursing education should be increased, not limited to conventional health-care professionals. A great gap exists between simulations under restricted conditions that have been practiced in conventional nursing education and those in the actual clinical site, thus creating a burden on nurses and patients. If a simulator that approaches real clinical situations can be developed, it will not only contribute to lessening the burden on nurses but also improve the quality of nursing care. The ESTE-SIM, which simulates endotracheal suctioning, can measure the movements of the suction catheter inserted in the trachea. The measurement information is used to estimate the progress of the nursing maneuver, which is then used to reproduce vital reactions, including dynamic facial expression changes based on projection mapping and monitor-displayed vital signs. To design and control the vital reactions, a mathematical model to determine the behavior of the simulator is formulated based on the actual measurement data of the vital reactions of patients and the experiential knowledge of nurses. By integrating these element technologies, we developed a novel interactive nursing education simulator capable of recreating typical vital reactions that occur during the basic endotracheal suctioning maneuver.