A model that predicts the stiffness degradation in multidirectional reinforced laminates due to off-axis matrix cracks is proposed and evaluated using data from fatigue experiments. Off-axis cracks are detected in images from the fatigue tests with automated crack detection to compute the crack density of the off-axis cracks which is used as the damage parameter for the degradation model. The purpose of this study is to test the effect of off-axis cracks on laminate stiffness for different laminate configurations. The hypothesis is that off-axis cracks have the same effect on the stiffness of a ply regardless of the acting stress components as long as the transverse stress is positive. This hypothesis proves to be wrong. The model is able to predict the stiffness degradation well for laminates with a ply orientation similar to the one used for calibration but deviates for plies with different in-plane shear stress. This behavior can be explained by the theory that off-axis cracks develop by two different micro damage modes depending on the level of in-plane shear stress. It is found that besides influencing the initiation and growth of off-axis cracks, the stiffness degradation is also mode dependent