In this paper hydrogen generation and storage systems optimization, related to a very large size hydraulic plant (Itaipu, 14GW) in South America, is investigated using an original multilevel thermo-economic optimization approach developed by the Authors. Hydrogen is produced by water electrolysis employing time-dependent hydraulic energy related to the water which is not normally used by the plant, named “spilled water”.From a thermo-economic point of view, the two main aspects of the study are the optimal definition of the plant size and the whole system management. Both of them are strongly influenced by (i) spilled water energy variability related to its time-dependent distribution during the whole year, (ii) time-dependent electricity demand of Paraguay and Brazil (the owners of the Itaipu plant) electrical grids, and (iii) the hydrogen demand profile.The system analyzed here consists of a very large size hydrogen generation plant (hundreds of MW) based on pressurised water electrolysers fed with the so called “spilled water electricity”, the related H2 storage, and the H2 demand profile for Paraguay transport sector utilization.Since H2 plant optimal size is strongly correlated to optimal management and vice-versa, in this paper two hierarchical levels have been considered hour by hour on a complete year time period, in order to minimize capital and variable costs. This time period analysis is necessary to properly take into account spilled energy variability to find out H2 production system optimal size, optimal storage solution and best economical results.For the optimal storage size, two different solutions have been carefully investigated: (i) classical long time H2 physical storage using pressurised tanks at 200 bar; (ii) hybrid one using reduced size physical storage (one day time demand) where the energy to feed electrolysers is taken from electrical grid when spilled water energy is not available [Rivarolo M, Bogarin J, Magistri L, Massardo AF. Hydrogen generation with large size renewable plants: the Itaipu 14 GW hydraulic plant case. In: 3rd international conference of applied energy (ICAE), 16–18 May 2011, Perugia; 2011.]. For both the two solutions, time-dependent results are presented and discussed with particular emphasis to economic aspects, system size, capital costs and related investments. It is worthy to note that the results reported here for this particular H2 large size plant case represent a general methodology, since it is applicable to different size, primary renewable energy, plant location, and different H2 utilization.