Objective: Central venous catheters (CVCs) provide direct access to the central circulatory system, commonly used in hemodialysis and intensive care units for drug administration. Although uncertified for the procedure, CVCs are sometimes used for power injection of contrast medium (CM) during CT scans to avoid peripheral intravenous catheter placement. Previous studies suggest this practice is safe, but incidents are reported. This study aims to measure intraluminal pressure during CM injection through CVCs and assess its impact on the luminal surface to guide responsible clinical use. Materials and methods: An experimental in vitro test setup was developed. Four samples each of three different types of unused CVCs were used. Strain gauges were applied to the exterior walls of either the inflow or outflow lumen of the CVC. These gauges measured material deformation due to intraluminal pressure during CM injections at rates of 4.5 and 8 mL/s, each performed five times. Strain data were calibrated against known pressures in a static system. Three CVCs of each type were then pressurized until bursting, and one was subjected to microscopic analysis of the luminal surfaces. Results: Intraluminal pressures measured (97–545 kPa or 14–79 PSI) were below the burst pressure (779–1248 kPa or 113–181 PSI) in all instances. Strain regression analysis shows a statistically significant (p < 0.01) trend over 10 injections in all CVCs tested except one, indicating material fatigue. Surface microscopy revealed surface micro-cracks from repeated injections, suggesting material damage. Conclusions: The intraluminal pressures from power injections of CM are sufficiently low to prevent CVC bursting. While incidental use for CM injection appears safe, repeated use may cause material damage.