In the last decade, Meshless Methods have found widespread application in different fields of engineering and science. Beyond novelty, their mathematical simplicity and numerical accuracy have been the key of their rapid dissemination. Among meshless techniques, RBF (Radial Basis Functions) based methods can be simple and general to solve the problems related to multiple areas of applied physics and engineering. In the specific field of acoustics, there are usually two possible approaches for solving a problem: time- and frequency-domain. In this paper, the authors propose a local time-domain approach to establish an efficient methodology for the solution of large-scale acoustic wave propagation problems. For this purpose, a local interpolation scheme, based on the reproduction of the local wave field using RBFs (MultiQuadric and Gaussian), is implemented and its accuracy is verified against known closed-form solutions. An explicit time-domain marching procedure is adopted, and the quality of the numerical results is also compared with that obtained using standard space-time Finite–Difference schemes. Additionally, the RBF interpolation model is used to simulate the propagation of a Ricker pulse in two simple test cases, and applied to simulate a more complex configuration, corresponding to an underwater sound propagation problem. In this frame, the results are also compared with those computed using a fourth-order in space and second-order in time Finite–Difference scheme.