Hot Isostatic Pressing (HIP) is a manufacturing process for production of near-net-shape components, where models based on Finite Element Method (FEM) are generally used for reducing the expensive experimental trials for canister design. Researches up to date implement in the simulation a uniform powder relative density distribution prior HIPping. However, it has been experimentally observed that the powder distribution is inhomogeneous after filling, leading to a non-uniform tool shrinkage. In this study a comprehensive numerical model for HIPping of Ti-6Al-4V powder is developed to improve model prediction by simulating powder filling and pre-consolidation by means of a two-dimensional Discrete Element Method (DEM). Particles' dimension has been scaled up in order to reduce the computational cost of the analysis. An analytical model has been developed to calculate the relative density distribution from powder particle distribution provided by DEM, which is then passed in information to a three-dimensional FEM implementing the Abouaf and co-workers model for simulating powder densification during HIPping. Results obtained implementing the initial relative density distribution calculated from DEM are compared with those obtained considering a uniform relative density distribution over the powder domain (classic approach) at the beginning of the analysis. Experimental work has been carried out for validating the DEM (filling) and FEM (HIP) model. Comparison between experimental and numerical results shows the ability of the DEM model to represent the powder flow during filling and pre-consolidation, providing also a reliable values of the relative density distribution. It also highlights that taking into account the non-uniform powder distribution inside the canister prior HIP is vital to improve numerical results and produce near-net-shape components. (C) 2019 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.