Oil and gas well productivity can be affected by a number of different skin factors, the combined influences of which contribute to a well’s total skin factor. The skin caused by deviated wells is one such well-known factor. The present study aimed to investigate skin effects caused by deviated well slants when considering vertical-to-horizontal permeability anisotropy. The research employed computational fluid dynamics (CFD) software to simulate fluid flows in inclined wells through the injection of water with Darcy flow using 3D geometric formations. The present work investigates the effects of four main characteristics—namely, the permeability anisotropy, wellbore radius, reservoir thickness, and deviation angle—of open-hole inclined wells. Additional investigations sought to verify the effect of the direction of perforations on the skin factor or pressure drop in perforated inclined wells. In the case of an inclined open hole well, the novel correlation produced in the current study simplifies the estimation of the skin factor of inclined wells at different inclination angles. Our comparison indicates good agreement between the proposed correlation and available models. Furthermore, the results demonstrated a deviation in the skin factor estimation results for perforated inclined wells in different perforation orientation scenarios; therefore, existing models must be improved in light of this variance. This work contributes to the understanding and simulation of the effects of well inclination on skin factor in the near-wellbore region.