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The strengthening of existing steel structures against high-cycle fatigue (HCF) loading has become one of the most important topics of interest in structural rehabilitation. Apart from the conventional strengthening techniques that incorporate bulky and heavy steel reinforcements, the application of carbon fiber reinforced polymer (CFRP) composites has attracted much interest for the strengthening of fatigue-prone (or fatigue-damaged) steel members. Over the last two decades, considerable research studies have been conducted to further understand the static and/or fatigue behavior of CFRP-strengthened steel members. However, existing knowledge on the issue is more focused on the strengthening of small-scale steel members using nonprestressed CFRP patches subjected to the simple mode I (tensile mode) loading condition. Nevertheless, it is quite evident that a combination of modes I and II (shear mode), hereafter referred to as the mixed mode I/II loading condition, often acts on structural members; such a complex loading is responsible for the failure of fatigue-critical details. Although some limited research studies have been conducted on the mixed mode I/II fatigue behavior of bare mild steel, which is relevant for civil structural applications, the existing literature does not provide any solution for the strengthening of fatigue-cracked members subjected to mixed mode I/II loading condition. Therefore, the main objective of the current PhD work is to propose a strengthening design approach to arrest an existing mixed mode I/II fatigue crack in a structural steel member by using prestressed CFRP reinforcements. To achieve this objective, first extensive analytical and experimental studies are conducted to develop a viable prestressing system by comparing the performance of the prestressed bonded reinforcements (PBRs) with that of a novel prestressed unbonded retrofit (PUR) system. Second, a strengthening design approach is proposed for the mixed mode I/II fatigue crack arrest in existing structural steel members using the developed PUR system. Through the analytical formulation of mode I and II stress intensity factor ranges, a design model is proposed to determine the strengthening solution, including the required prestressing level and/or the cross-sectional area of the reinforcement, which would ensure the complete arrest of an existing mixed mode I/II fatigue crack in a steel member. The proposed model is validated by performing sets of stepwise HCF tests on reference unstrengthened and prestressed CFRP-strengthened precracked steel plates of grade S355J2+N under various mode mixities. From a practical point of view, it deemed necessary to develop a reliable system for the prestressed strengthening of real-scale metallic members. Therefore, an alternative configuration of the PUR system, named the flat prestressed unbonded retrofit (FPUR) system is developed for the strengthening of real-scale metallic I-girders using multiple prestressed CFRP plates. An analytical model is proposed to accurately determine the stress levels in a metallic I-girder strengthened with the developed FPUR system, and sets of real-scale pull-off tests, as well as static and fatigue four-point bending tests are conducted to confirm the excellent performance of the system. The practical application of the FPUR system is demonstrated for the strengthening of a 122-year-old roadway metallic bridge in Australia.