Corrosion and failure of steel strands have been observed in post-tensioned (PT), segmental concrete bridges (PT bridges, herein) in Florida and Virginia. In general, existing inspection and maintenance practices cannot detect, in a timely manner, the corrosion of strands in these types of bridges. New technologies have been developed to improve grouting procedures and corrosion protection of strands in PT bridges. However, their efficiency in protecting the strands from long-term corrosion is yet to be proven. Therefore, ensuring long-term safety/reliability of PT bridges is of significant concern and a better design approach to ensure long-term reliability could be beneficial, both from economic and safety perspectives. The AASHTO LRFD Specifications present reliability-based design procedures, which ensure high reliability for new PT bridges. However, these design procedures do not consider long-term losses in reliability due to the potential corrosion of strands and, therefore, may not guarantee sufficient reliability during the desired life of bridges. Based on the results of an extensive experimental program that tested 536 strand specimens and provided substantial data on the time-variant corrosion of strands under various environmental conditions, this paper summarizes some of the conclusions from the experiments and proposes a reliability-based design approach to ensure long-term reliability of PT bridges. This design approach is defined based on the reserve-reliability factor, Fβ-reserve. The term Fβ-reserve is defined as the ratio of the actual reliability index, β, at time t to the target reliability index, βtarget. Probabilistic strand capacity models reported in the recent literature, flexural demand and capacity formulations in the AASHTO LRFD Specifications, and structural reliability methods are used in the proposed design approach. This approach involves the assessment of long-term structural reliability during the preliminary design phases of PT bridges.