With the increased frequency of accidental and deliberate explosions, evaluating the response of civil infrastructure systems to blast loading has been attracting the interests of the research and regulatory communities. However, with the high cost and complex safety and logistical issues associated with field explosives testing, North American blast-resistant construction standards (e.g. ASCE 59-11 and CSA S850-12) recommend the use of shock tubes to simulate blast loads and evaluate relevant structural response. This study first aims at developing a simplified two-dimensional axisymmetric shock tube model, implemented in ANSYS Fluent, a computational fluid dynamics software, and then validating the model using the classical Sod’s shock tube problem solution, as well as available shock tube experimental test results. Subsequently, the developed model is compared to a more complex three-dimensional model and the results show that there is negligible difference between the two models for axisymmetric shock tube performance simulation; however, the three-dimensional model is necessary to simulate non-axisymmetric shock tubes. Following the model validation, extensive analyses are performed to evaluate the influences of shock tube design parameters (e.g. the driver section pressure and length and the expansion section length) on blast wave characteristics to facilitate a shock tube design that would generate shock waves similar to those experienced by civil infrastructure components under blast loads. The results show that the peak reflected pressure increases as the driver pressure increases, while a decrease in the expansion length increases the peak reflected pressure. In addition, the positive phase duration increases as both the driver length and expansion length are increased. Finally, the developed two-dimensional axisymmetric model is used to optimize the dimensions of a physical large-scale conical shock tube system constructed for civil infrastructure component blast response evaluation applications. The capabilities of such shock tube system are further investigated by correlating its design parameters to a range of explosion threats identified by different hemispherical TNT charge weight and distance scenarios.