The effect of microstructural aging on fatigue endurance of an API 5L X70 pipeline steel was evaluated. Results showed that fatigue life is clearly dependent on aging time and, hence, on microstructural degradation attributed to long-term service. This behavior is associated with the morphological evolution of cementite inside the ferrite grains, transforming from platelets to elongated and spherical particles, and finally into flaky particles. Similarly, cementite at the grain boundaries transforms into spheroidized cementite, facilitating the appearance of sliding bands and thus the extrusion and intrusion formation. The interactions of the fatigue crack tip with the microstructure during the crack propagation stage have a significant effect on fatigue life.