Among several nanoparticle properties, shape is important for their interaction with cells and, therefore, relevant for uptake studies and applications. In order to further investigate such characteristics, fluorescently labeled spherical polymer nanoparticles are synthesized by free-radical polymerization via the miniemulsion process. The spherical nanoparticles are subsequently submitted to controlled mechanical deformation to yield quasi-ellipsoidal polymeric nanoparticles with different aspect ratios. The uptake behaviors of spherical and non-spherical particles with equal volume are investigated qualitatively and quantitatively by electron microscopy, confocal laser scanning microscopy, and flow cytometry measurements. Non-spherical particles show fewer uptake by cells than their spherical counterparts with a negative correlation between aspect ratio and uptake rate. This is attributed to the larger average curvature radius of adsorbed non-spherical particles experienced by the cells.