In the oil and gas industry, various methods involving Computation Fluid Dynamics (CFD) are used to predict pressure losses while cleaning/operating horizontal drilling facilities with non-Newtonian fluids. Studies on the factors which influence such predictions are important to the successful design, development and operation of wellbores. The effects of hydrodynamic roughness along with eccentricity and rotational speed of a drill pipe are evaluated in the present study. Simulations are conducted using the commercial CFD code, ANSYS CFX 16.2 and the results are validated using experimental data. The current research shows that the pressure losses are strongly dependent on the equivalent roughness of a drilling annulus and, eccentricity and rotational speed of the drill pipe. The knowledge gained from this project is beneficial for designing, operating and troubleshooting drilling facilities.