Two-phase flow pressure drops through thin and thick orifices have been numerically investigated with air–water flows in horizontal pipes. Two-phase computational fluid dynamics (CFD) calculations, using the Eulerian–Eulerian model have been employed to calculate the pressure drop through orifices. The operating conditions cover the gas and liquid superficial velocity ranges Vsg = 0.3–4 m/s and Vsl = 0.6–2 m/s, respectively. The local pressure drops have been obtained by means of extrapolation from the computed upstream and downstream linearized pressure profiles to the orifice section. Simulations for the single-phase flow of water have been carried out for local liquid Reynolds number (Re based on orifice diameter) ranging from 3 × 104 to 2 × 105 to obtain the discharge coefficient and the two-phase local multiplier, which when multiplied with the pressure drop of water (for same mass flow of water and two phase mixture) will reproduce the pressure drop for two phase flow through the orifice. The effect of orifice geometry on two-phase pressure losses has been considered by selecting two pipes of 60 mm and 40 mm inner diameter and eight different orifice plates (for each pipe) with two area ratios (σ = 0.73 and σ = 0.54) and four different thicknesses (s/d = 0.025–0.59). The results obtained from numerical simulations are validated against experimental data from the literature and are found to be in good agreement.