Various training methods can be used to enhance the clinical self-efficacy of nurses caring for patients with the acute coronary syndrome (ACS). The present study aimed at investigating and comparing the effect of simulated patient and lecture training methods in the self-efficacy of nurses' clinical performance caring for ACS patients in 2016. This was a quasi-experimental study. The population consisted of 62 nurses working in cardiac intensive care units (CICU) of associated hospitals with Jahrom University of Medical Sciences. Sampling was done with the conventional method and divided into two groups; "lecture" and "simulated patient" education through random assignment. Data was collected with the Self-efficacy of Nurses' Clinical Performance Questionnaire before and after the intervention. Data analysis was performed with SPSS v16.0 software and paired and independent t-tests. There was a significant difference between pre- and post-intervention self-efficacy mean scores in the two groups (P<0.05). In addition, there was no significant difference between pre-intervention self-efficacy mean scores in the two groups (P>0.05). The simulated patient training method was more effective in enhancing nurses' self-efficacy in caring for ACS patients than the lecture method.