AbstractHigh‐speed countercurrent chromatography (HSCCC) is an emerging technique for preparative purification of a wide variety of solutes. Retention of the stationary phase is a crucial variable which is used for the derivation of the column efficiency, peak resolution, and solute retention. A mathematical model was proposed to describe the influences of operation conditions (flow rate, rotation speed), physical properties (density difference, viscosity, and interfacial tension), and instrument parameters (tube diameter, revolution radius) on the retention of the stationary phase, by building on the flow behavior of the two phases in the coiled column, laminar flow or droplet flow. The model parameters, together with the critical value at which the transition between the laminar flow and droplet flow occurs, were determined by the analysis of experimental data of the retention of the stationary phase measured in this work. Furthermore, the proposed model was used to predict the literature data of retention of the stationary phase for seven HSCCC apparatuses including preparative, semi‐preparative, and analytical types, with the coiled column material of PTFE and stainless steel, and for 16 two‐phase systems with 151 data points. The agreement between the predicted and the literature data is quite good with the total absolute deviation (AAD%) of 2.96% and the maximum deviation of 12.8%. © 2007 American Institute of Chemical Engineers AIChE J, 2007