Purpose: The purpose of this study is to describe the relationship between health literacy, preparedness for discharge, adherence to discharge instructions and difficulty coping after discharge among emergency department patients. Specific Aims: The Aims of this study were to: (1) describe the variability of health literacy of adult patients in an academic tertiary Emergency Department; (2) describe the relationship between health literacy, care transition, and perceived readiness for discharge on the patient’s adherence to discharge instructions and (3) explore whether health literacy, perceived preparation for discharge and care transition, predicts difficulty coping after discharge. Framework: Dr. Meleis’s Transitions Theory was used as a framework. Design: This is a prospective cohort study of adults treated and discharged from the ED. Results: Eighty five percent of the subjects completed the study (n = 132). Subjects satisfied with transition care (P = .025) and who felt more prepared for discharge (P = .035) had less difficulty coping. Subjects more satisfied with care transition were more likely to adhere to medication instructions (P = .029). The higher the satisfaction with discharge preparation, the less likely the subjects were to go to their follow-up appointment (P = 0.051). No associations were found with health literacy. Conclusion: Satisfaction with care transition during the discharge process and feeling well-prepared are related to less difficulty coping after discharge. Nurses have an opportunity to intervene and enhance the discharge experience. This may contribute to more positive outcomes after being seen in an emergency department.