- A theoretical model capable of predicting particle–particle collisions in multiphase flow of spray dryer is proposed. The multiphase flow is described by an Eulerian–Lagrangian formulation using Discrete Phase Model for the dispersed phase. The devised model of binary particle–particle collisions is based on hard-sphere approach for discrete particle interactions and O’Rourke’s probabilistic algorithm for collision detection. Such approach enables compatibility with stochastic nature of sprays and facilitates dealing with vast amount of particles residing in spray chambers. The developed collision model was incorporated as a subroutine into a commercially available CFD code ANSYS FLUENT via mechanism of user-defined functions. The results of performed 2D axisymmetric and 3D transient simulations of multiphase flow in a pilot-plant spray dryer accounting for both droplet–droplet and particle–particle collisions demonstrated the importance of including the particle–particle interactions. It was found that consideration of both droplet–droplet and particle–particle collisions narrows the predicted zone of simultaneous heat and mass transfer towards the central region of the spray dryer compared to the numerical simulations including only droplet–droplet interactions calculated by the ANSYS FLUENT built-in subroutine. At the same time, particle–particle collisions distributed dry particles over periphery of the spray dryer. Consequently, these conclusions affect estimated particle fouling on chamber walls which is one of the main spray drying operation problems. So far the implications of this fundamental multiphase flow analysis including particle–particle collisions are important both for constructing new spray dryers and optimization of the existing spray drying processes.