Summary Recent pilot studies in Colombian reservoirs have demonstrated the benefits of nanotechnology at improving heavy-oil mobility. Understanding the physical and chemical processes that occur in the reservoir during the injection/production of nanofluid is essential for the design of the stimulation operations. We developed a novel mathematical model for studying the behavior of nanoparticles injected into heavy-oil reservoirs. Adsorption of asphaltenes on the surface of the nanoparticle and their effect on the viscosity of crude oil is accounted for in the model formulation. In addition, nanoparticles are retained/mobilized as operating condition changes. The transport and retention models are coupled to a multiphase/multicomponent model. The finite volume method is used to solve the differential equations of the model. The resulting equations are solved using the Newton-Raphson method. Core-flooding tests were used to calibrate the model parameters. The model was used for simulating the deployment of nanofluids in oil wells.