Most wind turbine blades are assembled piece-by-piece onto the hub of a monopile-type offshore wind turbine using jack-up crane vessels. Despite the stable foundation of the lifting cranes, the mating process exhibits substantial relative responses amidst blade root and hub. These relative motions are combined effects of wave-induced monopile motions and wind-induced blade root motions, which can cause impact loads at the blade root’s guide pin in the course of alignment procedure. Environmental parameters including the wind-wave misalignments play an important role for the safety of the installation tasks and govern the impact scenarios. The present study investigates the effects of wind-wave misalignments on the blade root mating process on a monopile-type offshore wind turbine. The dynamic responses including the impact velocities between root and hub in selected wind-wave misalignment conditions are investigated using multibody simulations. Furthermore, based on a finite element study, different impact-induced failure modes at the blade root for sideways and head-on impact scenarios, developed due to wind-wave misalignment conditions, are investigated. Finally, based on extreme value analyses of critical responses, safe domain for the mating task under different wind-wave misalignments is compared. The results show that although misaligned wind-wave conditions develop substantial relative motions between root and hub, aligned wind-wave conditions induce largest impact velocities and develop critical failure modes at a relatively low threshold velocity of impact.