Fatigue tests were conducted to analyze the fatigue behavior and diameter growth of large-diameter coiled tubing (CT) under the combined loads of bending and internal pressure. The experimental results reveal that mechanical limitations on the allowable diameter growth mean that the effective working life of CT at high pressures is only a fraction of the available fatigue life. The finite element software abaqus is used to further research the changes in diameter growth and to analyze the sensitivity of CT diameter growth to the main influencing factors, including internal pressure, tubing outside diameter (OD), wall thickness, yield strength, and bending radius. For CT with a diameter larger than 2 in., the diameter growth is sensitive to the above factors. As the bending and straightening cycles increase, the OD of the CT increases in association with obvious ovalization deformation, and the increase in the OD is closely related to the internal pressure load. The redistribution of material causes the wall thickness of the CT to become universally thinner. The ovality of the CT and the uneven decrease in wall thickness reduce the resistance to external extrusion. Therefore, it is becoming increasingly necessary to account for diameter growth as one of the key elements when predicting CT life or determining when to retire a string from service.