Compassion fatigue is a syndrome defined by both mental and physical restlessness. Mindfulness intervention can enhance one's emotions with nonjudgmental awareness and greater consciousness of thoughts and feelings. This study aims to examine the effect of mindfulness intervention on compassion fatigue among nurses. A randomized controlled trial was conducted, recruiting 100 nurses from three hospitals and dividing participants into an intervention and a control group. Increased mindfulness awareness was found in the comparison group in the research. The intervention group's mean burnout level was significantly lower than the comparison group. Age, gender, marital status, household size, and household income were among the sociodemographic factors that significantly correlated with compassion fatigue, which was determined through burnout and secondary traumatic stress. Nurses reported significant levels of compassion fatigue; however, this was significantly decreased through mindfulness intervention.