This paper presents a novel design method to predict fatigue of flood gates due to dynamic wave loading. The accumulation of fatigue damage is predicted probabilistically over the entire lifetime of the structure rather than with a set of normative events. Load events are defined using a joint probability distribution of historical wind and water level data. The random phase-amplitude model is employed to obtain realisations of the wave state for every combination of environmental conditions. Linear wave theory and pressure-impulse theory are used to predict both quasi-steady and highly dynamic wave pressures. The stress response of the structure is predicted with a hybrid semi-analytical and finite element model. By applying a mode matching technique the fluid-structure interaction is solved in a computationally efficient manner. This facilitates the large number of simulations required for a comprehensive fatigue analysis without making concessions in the physical modelling. The fatigue damage is then evaluated with the linear Palmgren-Miner method by applying a rainflow algorithm. A Monte Carlo analysis is performed to estimate the expected fatigue lifetime of the structure. The modular structure of the model routine allows for easy adaptation to other situations where fatigue due to hydrodynamic loading is of interest. The design method is applied to a case study of a flood gate with an overhang inspired by the situation at the Afsluitdijk. Non-fundamental modes are taken into account without simplification of the fluid-structure interaction process and found to be governing for the fatigue damage for the studied case. Moreover, the interference of vibrations due to consecutive wave impacts is shown to have a significant influence on the outcome of the fatigue assessment. For the case study, the design method leads to a 10-20% reduction of the governing fatigue damage compared to a method commonly used in practice. At specific locations on the flood gate fatigue damage is found to be underestimated by current design methods. The presented design method is therefore found to be a significant improvement.@en