Thanks to the advancements in computer power and capability of Computational Fluid Dynamics codes, the amount of research work on the numerical simulation of slurry flows in pipelines has increased exponentially in few years, opening the way to the use of this approach for engineering purposes. The Two Fluid Model (TFM), in which both phases are interpreted as interpenetrating continua and solved in the Eulerian, cell-based framework, allows the best compromise considering the engineering requirements of computational efficiency, applicability, and accuracy. However, the solution of this model is affected by several numerical and modelling factors, and, even if good agreement is achieved between simulation results and experimental measurements, it might be difficult to trust the predictions outside the validation conditions, thereby limiting the engineering potential of the two-fluid approach. The fully-suspended slurry flow in horizontal pipes was numerically simulated using the TFM recently developed by one of the authors of this paper, and the computational results were compared to experimental data reported in the literature. It has been clearly demonstrated that, even in this simple geometry, many possible sources of inaccuracy and uncertainty come into play. Whilst assessing their role, best practice guidelines and consistency checks were proposed to improve the accuracy of the estimates and increase the reliability of the TFM solution. Afterwards, pipe size-up scaling tests and a careful specification of the applicability conditions provided further confidence to the use of the TFM as a tool for engineering design. Display omitted •Convergence and sensitivity assessment followed by calibration and validation.•Critical inspection of diffcult-to-measure parameters.•Investigation of pipe size-up scalability of a two-fluid model.•Precise specification of the application domain.•Development of best practice guidelines for slurry pipe flow simulation.