To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100–300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified using validated high-performance liquid chromatography methods. In-vitro elution was performed over 24 h using a USP 4 dissolution apparatus. Diameter measurements were performed using light microscopy. Time in suspension was considered as the time required for the microspheres to vacate 1/3 of the volume. All three microsphere types rapidly loaded irinotecan, with more than 95% loading at 1 h. In-vitro elution of irinotecan was rapid for LifePearl and DC Bead microspheres, with more than 98% elution at 1 h, and delayed for Tandem microspheres, with about 70% elution at 6 h. After loading with irinotecan, the average diameter of LifePearl and DC Bead microspheres was reduced by 9 and 18%, respectively, and was unchanged for Tandem microspheres. All three microsphere types lost 4–6% of the loaded irinotecan almost immediately upon placement in contrast: water and contrast: 5% dextrose, but further losses were minimal over 2 weeks. LifePearl microspheres remained longer in suspension (392±23 s) compared with DC Bead (154±13 s, P<0.001) and Tandem (198±19 s, P<0.001) microspheres. All three microsphere types load irinotecan rapidly. LifePearl and DC Bead microspheres elute irinotecan rapidly. Elution is delayed with Tandem microspheres. LifePearl microspheres show the longest time in suspension.