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