Background: Post-traumatic stress disorder (PTSD) is one of the most prevalent mental health issues among emergency nurses, particularly in the aftermath of the COVID-19 pandemic. However, there is a scarcity of empirical studies on improving PTSD and related symptoms. Objective: To investigate the effectiveness of the mindfulness-based stress reduction (MBSR) program in reducing PTSD symptoms, emotional exhaustion, and coping styles among emergency nurses. Methods: A randomized clinical trial was conducted with 74 emergency nurses experiencing symptoms of PTSD who were recruited from two hospitals. Participants were randomly assigned to either the intervention group (n=38) or the comparison group (n=36) using a random number calculation procedure. The intervention group received an 8-week MBSR program, while the comparison group had the option to receive the same training upon completion of the study. Self-reported data on mindfulness, PTSD symptoms, emotional exhaustion, and coping styles were evaluated at baseline, after treatment, and 1-month of follow-up. Results: Participants in the MBSR group showed a significant improvement in PTSD symptoms (M(I-J)=-7.789, P<0.001, 95% CI=3.642~11.937), emotional exhaustion (M(I-J)=4.763, P=0.004, 95%CI=1.274~8.253) and mindfulness (M(I-J)=-7.421, P<0.001, 95%CI=-12.349~2.493) after treatment. These effects were sustained up to 1-month follow-up. No significant improvement in coping style was observed in any of the subjects. Conclusion: MBSR is feasible and effective in reducing symptoms of PTSD and emotional exhaustion among emergency nurses. However, it has a lesser effect on coping styles. MBSR has the potential to alleviate the psychological impact of occupational stress on nurses.