Burnout of nurses at university hospitals was analyzed in relation to their personality characteristics and coping behaviors. A self-administered questionnaire regarding burnout (the Copenhagen Burnout Inventory), work-related stressors (the Nursing Job Stressor Scale), personality characteristics (Short-Form Eysenck Personality Questionnaire-Revised), and coping behaviors (the short Japanese version of Brief COPE) was used. We obtained answers from 778 nurses (response rate: 94.9%), and analyzed 707 female registered nurses. Multiple regression analysis showed that neuroticism was more closely related to personal, work-related, and client-related burnout than extroversion. Covariate structure analysis revealed that among the nurses with high neuroticism and low extroversion, client-related burnout was found to be correlated with stressors in relation to conflict with patients and with positive coping behaviors. Among the nurses with low neuroticism and high extroversion, client-related burnout correlated with the coping behavior of behavioral disengagement and conflict with patients. In both groups, an increase in quantitative workload was associated with a higher score for stressors arising from conflict with patients, leading to client-related burnout. These results suggest that acquisition of skills to cultivate appropriate coping behaviors might be useful for reducing client-related burnout in relation to nurses' personality characteristics. These findings need to be further endorsed by intervention studies.