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The determination of the nonlinear response of structural members subjected to a close-in explosive threat is challenging. There are various ways to quantify the blast resistance and mode of failure of a structural member, e.g. experimental testing which is expensive and time-consuming, or high-fidelity finite element analysis which is also time-consuming. The familiar analytical approach using an equivalent single-degree-of-freedom (SDOF) system is much less costly, however, as will be shown in this paper, may lack accuracy. Based on an extensive study of the nonlinear response of a ground-floor column of a high-rise building subjected to close-in explosive threat, using nonlinear explicit finite element analysis as well as analytical single-degree-of-freedom (SDOF) system approach, the source of inaccuracy of the analytical approach is identified, and an empirical approach using Multivariable Polynomial Regression (MPR) is established. The paper presents a head-to-head comparison of the results produced by finite element analysis, the SDOF system analysis, the empirical approach, and experimental test data to emphasize the accuracy and time-efficiency of the proposed approach. The approach has the potential to establish itself as a time-efficient preliminary vulnerability assessment methodology of structural members subjected to close-in blast loading. [ABSTRACT FROM AUTHOR]