Compared with the earlier isotope separation systems built in Canada, Europe and the USA, the ITER system must accommodate several simultaneous feeds at the extremities of the distillation cascade and process a wide range of operating requirements resulting from the evolving research and technology testing program.1 Even after the program is defined, sufficient flexibility must be retained to accommodate changes expected due to the experimental nature of initial ITER operation. The reliable performance of the ITER water detritiation and isotope separation systems (ISS) and their flexibility must be achieved with minimum tritium inventory and maximum safety. This has required optimization of the system design and improvements in hardware designs for distillation columns, heat exchangers and feed polishing systems. Also the relatively high tritium concentration in water necessitated a new design approach for this part of the process namely the vapour phase catalytic exchange. The new hardware designs simplify the process flow sheet and the ISS cold box internal layout and its external configuration. This paper describes the design features of the ITER Water Detritiation and Isotope Separation system and the parameters that have had the most significant impact on the design.