Introduction Infusion therapy is challenging and dosing errors may occur due to physical phenomena related to the infusion hardware, despite the use of accurate syringe pumps. These errors typically occur after interventions, such as the exchange of a syringe. We aimed to characterize and quantify dosing errors due to a syringe exchange in relation to physical properties of infusion hardware. Methods An analytical simulation model was used to investigate dosing errors due to two different syringe exchange protocols (variations). Each protocol involved a fast syringe pump, containing a non-critical medication, and a slow syringe pump, containing a critical drug. The protocols were also reproduced in in vitro experiments to verify the simulation results. In addition, impact of syringe size, infusion set compliance, catheter diameter and the duration of the syringe exchange procedure on the quantity of the dosing errors was investigated. Results The syringe exchange of the slow pump resulted in an additional delay of up to 3536 seconds due to backflow. Syringe exchange of the fast pump resulted in an undiluted volume of critical drug (0.17 ml) accumulated in the infusion system, which may result in a dosing error rate of 2400 %. The quantity of the dosing errors are related to the syringe exchange duration; however, impact of infusion hardware properties is generally larger. Smaller syringes, catheters with larger diameters and less compliant infusion systems in general give rise to smaller dosing errors during a syringe exchange. If both lines are clamped, additional dosing errors can be prevented. Conclusion Infusion hardware has a substantial impact on the dosing errors during a syringe exchange. Clamping or blocking the infusion lines using, e. g. stopcocks, on all infusion lines during a syringe exchange is essential.