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Reinforced concrete (RC) columns, being axial-bearing components in buildings, are susceptible to damage and failure when subjected to blast loading. The failure of these columns can trigger a progressive collapse in targeted buildings. The primary objective of this study is to investigate the failure characteristics of laboratory-scale RC columns subjected to localized blast loading. The columns, with a length of 1500 mm and an outer diameter of 100 mm, are reinforced with 6 mm diameter longitudinal bars and 2 mm diameter steel ties. The blast loading is generated using an explosive-driven shock tube (EDST) positioned in front of the mid-span of the RC columns with a 30 g and 50 g charge. To capture the global response of the RC columns, high-speed stereoscopic DIC is used in addition to LVDTs. Furthermore, an FE model is developed using LS-DYNA R10.0 and validated against the experimental data. The results show that the proposed FE approach is able to reproduce the applied blast loading and the failure characteristics of the columns. The relative difference in column mid-span out-of-plane displacement between the FE model and the average measured data lies below 5%. Finally, the gray correlation method is conducted to assess the influence of various parameters on the blast resistance of the RC columns.