Background: Hospital layout is one important factor affecting hospital service quality and, consequently, patient satisfaction. Generally, the layout is designed based on the experience of the hospital specialists without any systematic approaches. Purpose: Due to the increasing number of patients, the case study hospital has built a new multi-floor building to move its Outpatient Department (OPD) to operate there. Therefore, this study aims to apply the Activity Relationship Analysis (ARA) and simulation to design a new OPD layout. Methodology: Data of the previous system were analyzed using the ARA. The results were then used to design three scenarios (A, C, and D) and the other three scenarios (B, E, and F) were proposed by hospital specialists. Then, six layouts were evaluated using simulation tests and the efficiencies of the designs were measured by an average total service time per patient. Results: The simulation results showed that the average total service time of scenario A, D, E, and F were lower than scenario B and C. While the average total service time at the sub-service unit of D was the longest compared to scenario A, E, and F. These results demonstrated that scenario A, E, and F were the most efficient layouts. However, when considered thoroughly by the hospital specialists, scenario A was eventually selected. Conclusion: This study can contribute to scientific literature as it demonstrates the application of the ARA and simulation in the design of the multi-floor layout, an aspect under-researched in existing studies. This study also provides the practical implication suggesting that these techniques should be used together in the layout designs because they can help to determine the correctness and efficiency of the layout design before actual implementation.