In oil and gas drilling operations, predictions of pressure losses and cuttings concentration in the annulus are very complex due to the combination of interacting drilling parameters. Past studies have proposed many empirical correlations to estimate pressure losses and cuttings concentration. However, these developed correlations are limited to their experimental data range and setup, and hence, they cannot be applicable to all cases. CFD methods have the advantages of handling complex multiphase flow problems, as well as, an unlimited number of physical and operational conditions. The present study employs the inhomogeneous (EulerianEulerian) model to simulate a two-phase solid-fluid flow and predict pressure losses and cuttings concentration in eccentric horizontal annuli as a function of varying drilling parameters: fluid velocity, diameter ratio (ratio of inner pipe diameter to outer pipe diameter), inner pipe rotation speed, and fluid type. Experimental data for pressure losses and cuttings concentration from previous literature compared very well with simulation data, confirming the validity of the current model. The study shows how reliable CFD methods can replicate the actual, yet complex oil and gas drilling operations.