Positron Emission Particle Tracking is a powerful and noninvasive technique and has been successfully used in a wide range of fundamental research and industrial applications. However, it is only capable of following a single tracer. This article presents a Multiple-Positron Emission Particle Tracking technique for tracking two freely moving particles in opaque systems and its application. The developed technique has been validated through tracking two stationary particles and two moving particles, respectively. The results showed that it is a reliable technique and can be potentially used to acquire more comparative information, such as the interactions and relative motions of particles with different sizes, densities, and material textures in multiphase systems. Tracking two polyethylene particles, labeled using F-18, in a cylindrical fluidized bed has been given as an example. The information obtained provides significant insights into phenomena in flow and mixing processes. (c) 2007 American Institute of Chemical Engineers.