Nursing students have limited opportunities to experience end-of-life care, so it is difficult for them to learn how to deliver it empirically. The use of simulations with standardized patients may be a way to provide realistic experience of end-of-life care for nursing students. The aim of this study was to evaluate the effectiveness of end-of-life care simulations with standardized patients in improving the knowledge, skill performance and self-confidence of undergraduate nursing students. Randomized controlled study. Japanese university nursing school. Thirty-eight students in the third year of the Bachelor's degree in nursing (simulation group = 20, control group = 18). After randomization to a simulation or control group, participants in the simulation group participated in an end-of-life care simulation with standardized patients. The primary outcome of a change in the knowledge score was assessed using a knowledge questionnaire, skill performance by completing Objective Structured Clinical Evaluations, and self-confidence related to end-of-life care by self-reported questionnaires. The simulation group improved significantly in knowledge, skill performance in physical assessment and psychological care, and self-confidence related to end-of-life care. The results of the two-way analysis of variance showed a significant interaction between groups and time (p = 0.000). Analysis of the simple main effect showed a significant difference (p = 0.000) between groups after the end-of-life care simulation and a significant difference (p = 0.000) over time in the simulation group. There were large effects on knowledge improvement (η2 = 0.372), physical assessment (η2 = 0.619), psychological care skill performance (η2 = 0.588), and self-confidence in both physical assessment (η2 = 0.410) and psychological care (η2 = 0.722). End-of-life care simulation with standardized patients would be an effective strategy to train nursing students, who have limited opportunities to experience end-of-life care.