Background: Pain has been integrated as the fifth vital sign that is a common health problem for emergency room patients. Although prior studies have addressed the effects of the pain-management knowledge of emergency room staffs on the quality of pain care, there is a dearth of research on pain management knowledge and on the factors that influence this knowledge. Purpose: To explore the knowledge of emergency room staffs regarding pain management and the factors that influence this knowledge. Method: This cross-sectional study used a self-developed questionnaire to survey a convenience sample of 201 physicians and nurses from three emergency rooms in northern Taiwan. Results: The average score for pain-management knowledge was 63.28 out of 100. Demographic variables including education level, professional specialty, and sources of pain education had significant effects on participants’ pain-management knowledge. Conclusions / Implications for Practice: The knowledge of emergency room staffs regarding pain management must be reinforced further in order to improve care quality. The factors identified that influence this knowledge may be referenced by hospitals in developing / revising pain-related continuing education, in developing pain management guidelines, and in setting the directions for future research on pain management.