Fatigue cracks were found on a series of end-coped crane runway girders after 14 years of service in a steel mill building in China. Two typical crane runway girders with different spans were studied in this paper. Finite element analyses were conducted to investigate the stress concentration at the coped ends. Analytical results showed the stress concentration effect was highly localized and the stress concentration factor decreased with increasing cope radius and decreasing total depth. The analytical results agreed well with the field measured data. Fatigue tests were conducted to determine the fatigue strength using eight 1/5-scaled end-coped girder specimens. Based on the analytical results and limited test data, the fatigue strength for a maximum principal stress range of 103 MPa at 2 million cycles may serve as a possible design guideline for end-coped crane runway girders using the conventional S-N curves. Procedures for design and evaluation of the fatigue life of end-coped crane runway girders are suggested.