A theoretical model for the cationization of plasticized wheat starch in a modular self-wiping co-rotating twin screw extruder was developed. Our objective was to build a model which would be able to predict the evolution of the cationization reaction along the screws, in relation with the processing conditions and the geometry of the twin screw extruder. Based on previous studies on reactive extrusion modeling, the present model takes into account the interactions occurring between the flow conditions encountered in the extruder and the kinetics of the reaction. It allows one to predict the influence of operating parameters such as reagent concentrations, feed rate, screw speed, and barrel temperature on the reaction extent. Depending on conditions, degrees of substitution in the range 0.01-0.05 are obtained, with efficiencies between 30 and 90%. A good agreement is found between theoretical results and experimental measurements, allowing future use of the model for optimization and scale-up purposes.