This paper presents results of a numerical and laboratory investigation into the mooring line forces and slow drift oscillations of large floating structures in multidirectional waves. A procedure for computing the spectral density of the second-order forces in random multi-directional waves based on the concept of a bidirectional, bifrequency quadratic transfer function is presented. Laboratory tests were carried out with a floating barge model, restrained horizontally by soft linear springs. The barge was subjected to random multi-directional waves with different degrees of directional spreading. The influence of wave directionality on the mooring line forces and low frequency motions is investigated by comparing results in unidirectional and multi-directional sea states with an identical frequency spectrum. The results indicate a significant reduction of the mean and standard deviation of the surge response, and an increased sway and yaw response. The mooring line forces were affected by wave directionality in a similar manner as the surge response.