This study presents a design criterion developed for fatigue strengthening of a 120-year-old metallic railway bridge in Switzerland and presents a pre-stressed un-bonded reinforcement (PUR) system developed to apply the strengthening. The PUR system uses carbon fiber reinforced polymer (CFRP) plates; however, unlike conventional pre-stressed CFRP reinforcement methods, preparation of the existing metallic bridge surface is not required. This decreases the time required for on-site strengthening procedures. The principle of the constant life diagram (CLD) and two fatigue failure criteria (Johnson and Goodman) are described. Analytical formulations are developed based on the CLD method to determine the minimum CFRP pre-stress level required to prevent fatigue crack initiation. The PUR system uses an applied pre-stress force to reduce the mean stress level (and stress ratio) to shift an existing fatigue-susceptible metallic detail from the ‘at risk’ finite life regime to the ‘safe’ infinite life regime. The applied CLD method is particularly valuable when the stress history of the detail is not known and it is difficult to assess the remaining fatigue life. Moreover, it is shown that the currently adopted approach in many structural codes which emphasizes stress range as the dominant parameter influencing fatigue life are non-conservative for tension–tension stress patterns (i.e., stress ratios of 0 < R < 1). Analyses show that the modified Johnson formula accurately reflects the combined effect of stress range, mean stress level, and material properties, and offers a relatively easy design procedure. Details of a retrofit field application on members of a riveted wrought iron railway bridge are given. A wireless sensor network (WSN) system is used for long-term monitoring of the on-site CFRP stress levels and temperature of the retrofitted details. WSN measurements indicate that increases in ambient temperature result in increased CFRP pre-stress levels.