The current solid acid catalyst based alkylation processes suffer from rapid deactivation of the catalysts which is affected by the shape and size of the catalysts, reactor configuration and the reactants’ feeding pattern. In this work, the deactivation of the solid acid catalysts in alkylation of iso-butane with butene and the reactor performance are studied using the multi-scale mathematical models. A pseudo-steady state catalyst pellet level model, incorporating the alkylation and deactivation kinetics, is coupled to the transient model of back mixed reactor configurations like a single CSTR and CSTR-in-series. The effects of catalyst shape, initial acid strength of the catalyst, paraffin-to-olefin feed ratio on the conversion of the olefin, on the yield of alkylates and on the time required for complete deactivation of the catalyst are investigated. The role of the size of the catalyst particles on the types of deactivation mechanism is elucidated. The effect of contacting pattern of iso-butane and butene in the reactor on the catalyst life and on the alkylate yield is also presented.