The method for the prediction of extreme vertical wave bending moments on a passenger ship based on the hindcast database along the shipping route is presented. Operability analysis is performed to identify sea states when the ship is not able to normally operate and which are likely to be avoided. Closed-form expressions are used for the calculation of transfer functions of ship motions and loads. Multiple operability criteria are used and compared to the corresponding limiting values. The most probable extreme wave bending moments for the short-term sea states at discrete locations along the shipping route are calculated, and annual maximum extreme values are determined. Gumbel probability distribution is then fitted to the annual extreme values, and wave bending moments corresponding to a return period of 20 years are determined for discrete locations. The system reliability approach is used to calculate combined extreme vertical wave bending moment along the shipping route. The method is employed on the example of a passenger ship sailing across the Adriatic Sea (Split, Croatia, to Ancona, Italy). The contribution of the study is the method for the extreme values of wave loads using the hindcast wave database and accounting for ship operational restrictions.