Abstract: We propose a systematic approach for calibrating the interphase drag models used in mesoscale CFD simulations of gas-liquid flow through packed beds. The method uses packing specific liquid holdup and pressure drop data to find model coefficients that both minimize relative error in the two-phase momentum equations and ensure correct limiting single phase behavior of the model. The approach is demonstrated for three phenomenological drag models from the literature using data from a random Bialecki ring packing under counterflow conditions. Calibration results in a 2–3-fold reduction in the mean relative error for predicted pressure gradient/liquid holdup, relative to predictions with “standard” Ergun coefficients, when an idealized set of momentum equations are solved. The calibrated models are then implemented into a two-fluid CFD solver and used to perform a two-dimensional time accurate simulation of the same packed bed at high gas and liquid flowrates. The predicted mean flow properties are in very good agreement with macroscale experimental data, while the instantaneous liquid distributions show significant transient, axial and lateral nonuniformities.