A multi-scale reservoir simulation framework for large-scale, multiphase flow with mineral precipitation in CO2-brine systems is proposed. The novel aspects of this reservoir modeling and simulation framework are centered around the seminal coupling of rigorous reactive transport with full compositional modeling and consist of (1) thermal, multi-phase flow tightly coupled to complex phase behavior, (2) the use of the Gibbs-Helmholtz Constrained (GHC) equation of state, (3) the presence of multiple homogeneous/heterogeneous chemical reactions, (4) the inclusion of mineral precipitation/dissolution, and (5) the presence of homogeneous/heterogeneous formations. The proposed modeling and simulation framework is implemented using the ADGPRS/GFLASH system. A number of examples relevant to CO2 sequestration including salt precipitation and solubility/mineral trapping are presented and geometric illustrations are used to elucidate key attributes of the proposed modeling framework. (C) 2016 Elsevier Ltd. All rights reserved.