Abstract: With the increasing depth in oil and gas drilling, the downhole vibration of drill strings in ultra-deep wells is very complex and the stress state changes significantly with time. In order to ensure the safety of drill strings in ultra-deep wells, the dynamic fatigue failure characteristics of ultra-thin and ultra-long drill strings constrained by spatially deflected wellbores were studied, and the structure and working parameters of drill strings were optimized. Based on the actual wellbore trajectory, the collision characteristics of the drill string with the borehole wall were considered, and the dynamic characteristics of the drill string were obtained through finite element simulation analysis. The fatigue strength of the drill string in ultra-deep wells under the variable asymmetric cyclic stress state was studied according to the accumulated fatigue damage theory. According to actual field case, the dangerous cross-section of the drill string in ultra-deep wells was analyzed, and the variation law of fatigue strength of the drill string with rotation speed, weight on bit (WOB), and stabilizer position was studied. The research demonstrated that WOB and high rotation speed have a great effect on the fatigue strength of the drill string, and low rotation speed slightly affects the fatigue strength of the drill string. After the stabilizer is installed, the probability of fatigue failure of the bottom hole assembly (BHA) can be greatly reduced, and the stabilizer position has a significant effect on the fatigue strength of the drill string. The research results provide a theoretical basis for the optimization of the structure and drilling parameters of drill strings in ultra-deep wells.