In order to evaluate the structural integrity of the breech system used for a thick-walled cylinder subjected to pulsating high internal pressure, fatigue life simulation of a breech system was performed. A stress analysis of the breech was performed to locate the critical region vulnerable to crack initiation. Low-cycle fatigue behavior of the breech material was investigated to obtain the fatigue crack initiation properties. Elastic-plastic finite element stress analysis resulted in a stress concentration at the breech ring groove root. Strains at the breech ring and block were experimentally measured using strain gages and resulted in similar values compared to the calculated strains. Local strain approach was employed to estimate the fatigue life of the breech system for crack initiation at the groove root of the breech ring. Fatigue tests using simulation specimens were performed and an averaged fatigue life was obtained, showing a very good agreement with the calculated fatigue life within a factor of two.