Abstract A damage-based design procedure has been developed by the authors to predict the damage evolution and the stiffness degradation in polymeric composite laminates under fatigue loading. For a safe and reliable design against fatigue degradation and failure, the initiation of the main damage mechanisms (off-axis cracks, delamination and fiber failure) as well as their evolution are considered and suitable models are proposed for the quantitative assessment of the lifetime associated to each mechanism. In parallel, the stiffness degradation deriving from the damage evolution over the fatigue life is properly described. After the illustration of the overall damage-based strategy, the paper discusses in details the analysis and modelling of the off-axis crack initiation and propagation. The initiation of cracks in the off axis plies has been proved to be the consequence of a damage process occurring at the microscopic scale since the early stages of fatigue. On this basis, crack initiation prediction is based on the use of local stress parameters: Local Hydrostatic Stress, LHS, and Local Maximum Principal Stress, LMPS, depending on the local degree of multiaxiality of the stress state and accounting for the statistical distribution of the local laminate strength. The propagation phase is then quantified by using a conventional fracture mechanics approach. The model has been implemented in a Matlab procedure for the quantitative evaluation of the crack density in each ply of a laminate during its entire fatigue life. The knowledge of the crack density trend allows the description of the laminate stiffness evolution taking advantage of another model recently developed by the authors, valid for a generic laminate configuration and accounting for the interaction between cracks in the neighbouring plies.