A computational fluid dynamics (CFD) model of the two-phase flow is presented to simulate isothermal, turbulent, upward bubbly flow in a pipeline for the purpose of forecasting a mean pressure reduction along the pipe (a three-dimensional (3D) multiphase flow, by Eulerian–Eulerian strategy combined with population balance model (PBM)). A set of experimental data from the literature for water (liquid) and air (gas) in an isothermal pipe is used where the internal diameter of which is 200 mm; it tends to analyze radial void fraction and bubble diameter distributions as well as the axial pressure distribution of fluid flow. The CFD model is applied to grids of minimum control volumes. The interfacial forces, including nondrag and drag forces, where the former can be categorized into turbulent scattering, lift, and wall lubrication, have been noticed in simulations. The comparison between CFD forecasts with experimental data demonstrates that the coring phenomena plus observed wall peaking could be predicted with this CFD-PBM modeling approach. The primary aim of this study was to anticipate the axial pressure distribution of bubbly flow in the pipe by CFD modeling in a large vertical pipe. Acceptable agreement between models predictions and experimental data indicates that CFD can be a beneficial method for investigating pressure drop of an upward and multiphase flow.