<div><br></div><div> Today, autoinjectors are developed for more viscous drug solutions, which require larger forces for actuating the syringe and impose larger stresses on the drug solution during the administration of autoinjectors. We developed experimentally validated high-fidelity simulations to investigate the liquid jet formation, liquid slosh and cavitation during the insertion process of an autoinjector. </div><div> </div><div> The jet formed due to an acceleration-deceleration motion of syringe is found to be governed by the interplay between inertial, viscous, surface tension and gravitational forces. A scaling for the jet velocity and a criterion for the jet breakup in a simplified geometry are proposed.</div><div> </div><div> When the syringe accelerates and decelerates during the insertion, liquid slosh occurs and there is a vehement motion of the air-liquid interface. Here, we quantified the area of air-liquid interface and hydrodynamic strain rate, which increase with the air gap size, syringe velocity, tilt angle and inner wall hydrophobicity, and decrease with the solution viscosity and hardly change with the liquid column height and surface tension. The strain rate is not sufficient to unfold the protein and the air-liquid interface is more likely to cause protein aggregation.</div><div> </div><div> In a spring-driven autoinjector, the plunger is actuated by the impact of a driving rod, which generates a strong pressure wave and can cause cavitation inception. The cavtiation bubbles can be impeded by the syringe walls and form a re-entrant jet shooting toward the syringe wall. During the process, the protein molecules are focused in the jet, pushed toward the syringe wall and spread across the wall, which can be the reason for the protein aggregation and adsorption on the syringe walls. The impedance effects of the wall decreases with the wall distance and increases with the maximum bubble size. The maximum bubble radius also increases with the liquid column size and nucleus size and decreases with the air gap pressure. Since inertia effects dominate in the cavitation process, the liquid viscosity and surface tension hardly changes the cavitation bubble dynamics. Small bubbles can also form in the bulk, which may generate aggregates in the bulk solution. Bubbles in the cavitation bubble cloud may coalesce with nearby bubbles and induce a higher pressure at the collapse (up to 1000 bar). This high pressure can potentially generate hydroxyl radicals that oxidize the protein molecules.</div><div> </div><div> The current study presents a detailed picture of fluid flows in autoinjectors and provide recommendations for mitigating the liquid slosh and cavitation generated in syringes. The results can be combined with future experiments to understand the implications of fluid flows on protein drugs and the performance of autoinjectors.</div>