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Sections of cannon tubes with inner radius of 53, 60, and 78 mm were cycled from near zero to 100–300 MPa internal pressure until fatigue failure occurred. The failure locations were along 2-mm holes cut through the cannon wall at a 30-deg angle to the tube axis, for the purpose of evacuating combustion gases from the cannon after firing. The cannons had various amounts of autofrettage by overstraining, including 0, 30, 50, and 100 percent. The amount of overstrain affected both the initiation position of the fatigue crack along the evacuator hole and the measured fatigue life. Increasing the amount of overstrain moved the crack initiation from the tube inner radius toward a mid-wall position and significantly increased fatigue life. Fracture mechanics and solid mechanics-based calculations of fatigue life were performed for comparison with the measured lives. The calculations gave a good description of the measured life, taking account of tube configuration, applied pressure, amount of overstrain, stress concentration of the hole, crack size and shape, material fatigue crack rate behavior and yield strength, and pressure in the hole and on the crack surfaces. As with measured fatigue life, the calculated life was significantly affected by the amount of autofrettage of the tube. The ratio of outer to inner radius of the tube and the presence of pressure in the evacuator hole also had substantial effects on the calculated fatigue life.