Safety valves are installed on process equipment where pressure-rise would occur to prevent rupture of them in chemical plants. However, it is difficult to analyze pressure-rise behavior quantitatively during reaction runaway, especially, in case of occurrence of two-phase flow. It is necessary to apply experimental and analytical technical knowledge for the vent sizing. The vent sizing method for two-phase flow by reaction runaway has been developed by the Design Institute for Emergency Relief Systems (DIERS) established in 1987, and then ISO 4126-10 was published in 2010 and it got the global standard. However, the ISO model is assumed conservative analysis condition to prevent underestimation, and sometimes unrealistic results are obtained. In this study, detailed process dynamic simulation model to estimate accurate vent size was constructed in Aspen Dynamics, process simulation software. In order to construct dynamic simulation model, it is necessary to define reaction rates, mass balance including chemical reactions and flow rate from vent or exhaust gas line, and heat balance between before and after chemical reactions. These parameters regarding the runaway reaction were obtained through Advanced Reactive System Screening Tool (ARSST) experiments. As ISO-omega model is not contained in Aspen Dynamics, ISO-omega model constructed by Aspen Custom Modeler is coupled with Aspen Dynamics as a subroutine program. Process parameters such as temperature, pressure and liquid level in process equipment are calculated comprehensively, and effect of exhaust gas line is also considered in this model. In order to confirm the validation of the results of detailed simulation model, a 40-mL-scale small test apparatus with a safety valve was developed. The maximum pressure with each diameter of safety valve was observed experimentally and they were good corresponding to the results of detailed simulation. Furthermore, this experimental method would be expected to estimate the vent size directly without the complicated analysis such as the ISO method or a detailed simulation model. The combination of case studies of the experiment and simulation also provides various additional knowledge, such as identification of the composition in a reactor in which a less violent runaway reaction occurs or the process condition for which a runaway reaction does not inherently occur. This study would contribute to the design of resilient processes for process upsets and will lead to sustainable and economical design.