AbstractHigh‐speed countercurrent chromatography (HSCCC) is a versatile technique for preparative separations of a wide variety of solutes. For optimization of operating conditions, prediction of separations, and scale‐up study, a model is needed to describe the effluent concentration profile, which determines the separation efficiency (mass transfer, mixing, and partitioning) and the resolution between peaks. A transfer‐dispersive model is proposed to describe the effluent profile based on the assumption that the retention of a peak is caused by partitioning over two phases, and peak broadening is caused by axial dispersion and mass transfer limitation. In this work, mass transfer was investigated by comparing model simulations to experimental data. One generalized correlation of overall mass transfer coefficients was derived. Based on the correlations of axial dispersion coefficients in our previous work and mass transfer coefficients in this study, the model predicts the elution concentration profile well. Furthermore, separation criteria were proposed to predict the separation of two adjacent solutes, and they were verified using literature data. © 2010 American Institute of Chemical Engineers AIChE J, 2011