Background Self-efficacy in resuscitation is influenced by various educational models, including high-fidelity simulation (HFS). Method Sixty-two nurses who were enrolled in an Advanced Cardiac Life Support (ACLS) course using HFS were recruited for this pretest-posttest, quasi-experimental study. Self-efficacy was assessed three times-twice via the participants' self-report and once via the instructor's assessment-using the Resuscitation Self-Efficacy Scale (RSES). Results The four dimensions of self-efficacy-recognition, debriefing and recording, responding and rescuing, and reporting-improved after the HFS education (t = 4.89, SE = 1.84, p < .001, confidence interval [-12.7, -5.33]). The instructor's scoring was higher than the participants' scoring in two of the four dimensions. The score on the ACLS written examination was positively correlated with the posttest RSES score (r = 0.303, p = .017). Despite minimal variations between demographic subgroups, nurses who had never been involved in resuscitation exhibited a significant improvement in self-efficacy after the HFS ACLS education (t = 4.72, SE = 2.54, p < .001, confidence interval [-17.3, -6.7]). Conclusion Self-efficacy can be a core measurable outcome that gauges nurses' clinical competency concerning HFS education for ACLS. [.