Healthcare sectors face multiple threats, and the hospital emergency department (ED) is one of the most crucial hospital areas. ED plays a key role in promoting hospitals' goals of enhancing service efficiency. ED is a complex system due to the stochastic behavior of patient arrivals, the unpredictability of the care required by patients, and the department's complex nature. Simulations are effective tools for analyzing and optimizing complex ED operations. Although existing ED simulation models have substantially improved ED performance in terms of ensuring patient satisfaction and effective treatment services, many deficiencies continue to exist in addressing the key challenge in ED, namely, long patient throughput time. The patient throughput time issue is affected by causative factors, such as waiting time, length of stay, and decision-making. This research aims to develop a new simulation model of patient flow for ED (SIM-PFED) to address the reported key challenge of the patient throughput time. SIM-PFED introduces a new process for patient flow in ED on the basis of the newly proposed operational patient flow by combining discrete event simulation and agent-based simulation and applying a multi-attribute decisionmaking method, namely, the technique for order preference by similarity to the ideal solution. Experiments were performed on three actual hospital ED datasets to assess the effectiveness of SIM-PFED. Experimental results revealed the superiority of SIM-PFED over other alternative models in reducing patient throughput time in ED by consuming less patient waiting time and having a shorter length of stay. The findings also demonstrated the effectiveness of SIM-PFED in helping ED decision-makers select the best scenarios to be implemented in ED for ensuring minimal throughput time while being cost effective.