Monodisperse mesoporous silica (mSiO 2) coated superparamagnetic iron oxide (Fe 3O 4@mSiO 2) nanoparticles (NPs) have been developed as a potential magnetic resonance imaging (MRI) T 2 contrast agent. To evaluate the effect of surface coating on MRI contrast efficiency, we examined the proton relaxivities of Fe 3O 4@mSiO 2 NPs with different coating thicknesses. It was found that the mSiO 2 coating has a significant impact on the efficiency of Fe 3O 4 NPs for MRI contrast enhancement. The efficiency increases with the thickness of mSiO 2 coating and is much higher than that of the commercial contrast agents. Nuclear magnetic resonance (NMR) relaxometry of Fe 3O 4@mSiO 2 further revealed that mSiO 2 coating is partially permeable to water molecules and therefore induces the decrease of longitudinal relaxivity, r 1. Biocompatibility evaluation of various sized (ca. 35-95 nm) Fe 3O 4@mSiO 2 NPs was tested on OC-k3 cells and the result showed that these particles have no negative impact on cell viability. The enhanced MRI efficiency of Fe 3O 4@mSiO 2 highlights these core-shell particles as highly efficient T 2 contrast agents with high biocompatibility.