High clearance sprayer is a high-efficiency pesticide application machine in orchard management. In this paper, operational safety of high clearance sprayers is validated by using finite element simulation and vibration testing. The 3D model of the frame is simplified by using shell units instead of solid units, the static performance of high clearance sprayer frames under static full load and ultimate torsional conditions was studied by means of finite element simulation tests, the mechanical properties of the frame under step excitation were studied by multi-body dynamic simulation test. The simulation results show that, at a safety factor of 1.5, the maximum stress extremes in the frame are within the safe permissible stress range. During the dynamics analysis, a tire-ground contact simplified model was proposed. The results of the modal analysis show that the inherent frequency distribution of the high clearance sprayer is compact, and the vibration test has measured a large difference between the engine vibration frequency with the inherent frequency of the frame, this means that resonance will not occur. The theoretical analysis shows that the designed high clearance sprayer meets the requirements of large cross-row field operations, the study provides a reference for the overall design of the high clearance sprayer.