Accurate pressure drop estimation is vital in wellbore hydraulic design. The present study investigates the effects of diameter ratio, fluid velocity, fluid type, fluid rheology and drillpipe rotation speed on pressure drop in eccentric horizontal wellbore with the presence of cuttings using computational fluid dynamics (CFD). The drillpipe is positioned at eccentricity of 0.623 and rotates about its own axis at 80 rpm and 120 rpm. The diameter ratio varies from 0.64-0.90. Results show significant increase in pressure drop with increasing fluid velocity and diameter ratio. Increase in drillpipe rotation speed from 80 rpm to 120 rpm shows insignificant effect on pressure drop for both Newtonian and non-Newtonian fluids. Non-Newtonian fluid exhibited large pressure drop compared to Newtonian fluid especially at low fluid velocities. Fluid rheology effects are also discussed. Experimental data confirmed the validity of the current model setup with a mean percentage error of 0.84. Copyright © 2015 Inderscience Enterprises Ltd.