This thesis aims to develop a comprehensive usable engineering design approach to the fatigue analysis of threaded connections. Although primarily concerned with the fatigue-fracture mechanics behaviour of screw threads, a broad review of stress analysis investigations in such connections is reported. Connection types, their functions and standardisation authorities are presented with the purpose of familiarising the reader with the subject and the options available to the design of threaded fasteners. Fatigue crack initiation is discussed with reference to the specific setting of a critical thread root. A crack initiation model is adapted for employment in thread root design. A novel weight function approach is developed for use in the determination of stress intensity factors for threaded connections. A generic solution is proposed valid for the fatigue crack growth from any thread root under any symmetrical stress system. Its development and discussion is examined in detail, remaining close to its proposed application. Two engineering situations where the chief structural components are comprised of threaded members are taken as case studies. The background to each situation is elaborated in detail and full-scale fatigue tests were conducted on the critical components. In all, fourteen full-scale tests under constant and variable amplitude loading are reported. The results of these are analysed and used to validate the fatigue crack initiation and propagation models. Useful observations which are helpful to understanding the fracture mechanisms operating during the fatigue of threaded connections are reported. Material and environmental considerations are examined and a survey of relevant materials and their behaviour in environments associated with threaded fasteners is presented. The merits or otherwise of some common engineering practices are discussed with regard to fatigue. A method has been developed for predicting fatigue life in large threaded connections under random loading. Experimental results have been gathered on two types of components used on certain oil rigs, tether joints and drill strings. The agreement found between prediction and experiment is appreciably better than by previous methods of analysis and also points to aspects open to further improvement.