Background Nurses’ job satisfaction affects how they feel about their work, their commitment, their relationships with patients and colleagues and ultimately the quality of care they provide. Beyond the many aspects of quality of work life, another factor that is likely to affect nurses’ job satisfaction is clinical empathy.

Aim To investigate the direct and indirect effects of quality of work life on nurses’ job satisfaction, with clinical empathy as a mediating factor.

Methods This was a quantitative cross-sectional study using a descriptive research design along with path analysis. The study population included all nurses working in the emergency departments of hospitals in Sanandaj, Iran. The short form of the Minnesota Satisfaction Questionnaire, the Quality of Work Life questionnaire and the health professional version of the Jefferson Scale of Physician Empathy were used to collect data. A total of 480 nurses were approached, 430 questionnaires were received, and 400 complete questionnaires were included in the data analysis.

Results The results showed that participants’ quality of work life had a direct and significant effect on their job satisfaction. In addition to its direct effect on job satisfaction, quality of work life also affected participants’ job satisfaction indirectly through the mediation of clinical empathy.

Conclusion Paying attention to the factors that affect nurses’ quality of work life and promoting high levels of clinical empathy among nurses can increase their job satisfaction and therefore the quality of care they provide.