Demands for health care are becoming overwhelming for healthcare systems around the world regarding the availability of resources, particularly, in emergency departments (EDs) that are continuously open and must serve immediately any patient who comes in. Efficient management of EDs and their resources is required more than ever. This could be achieved either by optimizing resource utilization or by the improvement of hospital layout. This paper investigates, through data-driven simulation alternative designs of workflows and layouts to operate the ED of the Uppsala University Hospital in Sweden. Results are analyzed to understand the requirements across the hospital for reduced waiting times in the ED. The main observation revealed that introducing a new ward dedicated to patients having complex diagnoses with a capacity of less than 20 beds leads to lower waiting times. Furthermore, the use of data-mining was of great help in reducing the efforts of building the simulation model.