Accurate simulation of water distillation system for oxygen-18 (O-18) isotope separation is necessary to guide industrial practice, since both deuterium (D) and oxygen-18 isotope get enriched and interfere with each other. In the present work, steady-state and dynamic distillation models are established based on a classic method and a cascade distillation system with 5 towers is introduced to test the models. The theoretical expressions of separation factor alpha(H/D) for protium/deuterium and separation factor alpha(16)(18)(O/)(O). for oxygen-16/oxygen-18 were derived, with the existence of deuterium and oxygen-18, respectively. The results of the steady-state simulation by the classical method proposed in the present work agreed well with the results of the lumping method. The dynamic process could be divided into 5 stages. Impressively, a peak value of product withdraw was observed before the final steady state, which was resulted from the change of O-16/O-18 separation factor and isotope distribution. An interesting low concentration zone in the towers of T2-T5 existed at the beginning of the dynamic process and it required industrial evidence. (C) 2016 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.