Asphaltene is a group of complex compounds commonly present in petroleum reservoir fluids. It is conceivable that asphaltenes strongly interact with water through hydrogen bonding, affecting phase behavior of water/oil mixtures with/without forming an asphaltene-rich phase. In this research, the cubic-plus-association equation of state (CPA EOS) is applied to multiphase behavior resulting from self- and cross-associations of asphaltenes and water in petroleum fluids. This article also presents a new correlation for binary interaction parameters for water with n-alkanes for the CPA EOS by using three-phase data for water/n-alkane binaries. A method is proposed to characterize mixtures of asphaltene-containing oil with water using the CPA EOS. Results show that the CPA EOS can represent multiphase behavior for water/oil mixtures with up to four equilibrium phases: asphaltene-rich, solvent-rich, aqueous, and vapor phases. Case studies include bitumen/water mixtures, involving asphaltene-water emulsion, water solution in bitumen, and their continuous transition with varying temperature. (c) 2018 American Institute of Chemical Engineers AIChE J, 64: 3429-3442, 2018