<p>Cold expansion was an effective method to prolong the fatigue life of open hole structures, and the mandrel insertion section shape was vital for the cold expansion quality. Therefore, in this study, numerical simulations and experimental tests were conducted to investigate mandrel profile effects on direct cold expansion fatigue behaviors of titanium open hole structures. The different mandrel insertion section shapes were designed, and three typical cold expansion sizes were considered. Results showed the peak resistance force decreased with increasing front taper angle and increasing curvature. The bulge at the exit face was more pronounced than that at the entrance face. The maximum residual tangential compressive stress was observed in the middle region along the thickness direction. The mandrel profile had an obvious influence on the unevenness of axial residual stress. The specimen strengthened by a mandrel with a front taper angle of <i>α</i> = 15° showed the smallest axial residual stress gradient and the best fatigue performance, with the fatigue life increasing by 86% compared to the un-strengthened specimen. The fatigue sources of all strengthened specimens were located at the entrance face and exit face. The fatigue band width of the strengthened specimen at the fatigue source region was smaller than that of the un-strengthened specimen.</p>