The University of Nebraska's I-girders, known as NU girders, are precast prestressed concrete girders that have unique characteristics. NU girders have a wide top flange (48.2 in) to provide a better platform for workers and shorter span for deck; and a wide and thick bottom flange (38.4 in) to accommodate a large number of prestressing strands. The depth of NU girders varies from 20.3 in. to 63.6 in. to allow the construction of bridges. that spans up to 210 ft with a high economic competency. These unique characteristics significantly affect the flexure and shear resistance of NU girders, and consequently, influence their reliability when the uncertainty of loads, material properties, and fabrication parameters are considered. This paper presents the reliability analysis of NU girders designed using the strength I limit state of the AASHTO LRFD bridge design specifications. Resistance models are developed for several types of NU girders (NU1600, NU1800, and NU2000) and considering different combinations of girder span (120 to 200 ft) and girder spacing (8 to 12 ft). The variability of flexure and shear resistance is calculated based on the uncertainty of: i) material properties, such as cast-in-place concrete strength, precast concrete initial and final strength, reinforcing steel yield strength, and prestressing strands ultimate strength; and ii) fabrication parameters, such as the dimensions of concrete sections, area of reinforcing steel, and area of prestressing strands. Load models are developed to account for the uncertainty in dead load, wearing surface load, live load, and impact load. The calculated reliability indices are examined for consistency and compared against the target reliability index for various combinations of girder type, span, and spacing.