Intensive computation time is required to simulate images of electronic portal imaging device (EPID) using Monte Carlo (MC) technique, limiting the development of applications associated with EPID, such as mega-voltage cone-beam computed tomography (MV-CBCT). In this study, a fast, accurate simulation strategy for MV-CBCT utilizing the FastEPID technique has been developed and validated. During FastEPID simulation, photon detection was determined by pre-calculated photon energy deposition efficiency (η) and particle transport within the EPID was replaced with a pre-calculated optical photon spread function. This method is capable of reducing the time required for EPID image simulation by a factor of 90-140, without compromising image quality. MV-CBCT images reconstructed from the FastEPID simulated projections have been validated against measurement in terms of mean Hounsfield unit (HU), noise, and cupping artifact. These images were obtained with both a Catphan 604 phantom and an anthropomorphic pelvis phantom, under treatment beam energies of 2.5 MV, 6 MV, and 6 MV flattening filter free. The agreement between measurement and simulation was excellent in all cases. This novel strategy was capable of reducing the run time of a full scan simulation of MV-CBCT performed on a CPU cluster to a matter of hours, rather than weeks or months required by a conventional approach. Multiple applications associated with MV-CBCT (e.g. imager design optimization) are anticipated to gain from the implementation of this novel simulation strategy.