The objective of this work is to investigate the influence of particle properties on the reactivity of Ni-based oxygen carriers in chemical-looping reduction. On the basis of a particle model, which considers the effects of internal, interparticle and external diffusion and reaction kinetics for Ni-based chemical-looping systems, thermogravimetric reactivity investigations are analyzed and interpreted. The challenge addressed is to quantify the contribution of variations in particle size, microstructure, and chemical deactivation on oxygen carrier reactivity. For a range of particle sizes, intraparticle diffusion is quantified and shown to be accurately captured by the model. Therefore, optimal oxygen carriers can be designed to minimize diffusion limitations, while satisfying fluidization and pressure drop requirements. The effect of gradual changes in the oxygen carrier microstructure due to redox cycling is analyzed through case studies and sensitivity analyses of their effect on reactivity. The framework of this analysis assumes that by incorporating these measured changes, it is possible to explain chemical-looping performance over the lifespan of the oxygen carrier and eventually design optimal systems. Experimental data from the literature and obtained in this work are utilized to provide insights on the contributions of particle size, pore size, spinel formation and surface area changes on reactivity. Experimental controversies in terms of the effect of redox cycling on chemical-looping performance are analyzed and shown to be the natural consequence of the transient changes in oxygen carrier properties. (C) 2014 Elsevier Ltd. All rights reserved.