The purpose of this study was to determine the influence of different materials of intraocular lenses (IOLs) on human lens epithelial cell behavior, including adhesion, migration, proliferation, apoptosis, and epithelial-mesenchymal transdifferentiation (EMT) in vitro. Human lens epithelial cells (SRA 01/04) were grown on hydrophobic acrylic (Acrysof), polymethylmethacrylate (PMMA), and silicone IOLs. Cellular adhesion, migration, proliferation, and apoptotic assays were performed to assess cell behavior. The expression of EMT markers (fibronectin and type I collagen) produced by cells on IOLs was determined by immunoblotting and immunocytochemistry. Human lens epithelial cells exhibited preferred adhesion and reduced apoptosis when cultured on acrylic IOLs, in comparison to PMMA and silicone IOLs. Cells grown on acrylic lenses formed a confluent epithelial monolayer. Migration of lens epithelial cells under the acrylic lens was substantially blocked in an in vitro assay. In contrast, cells grown on PMMA and silicone lenses displayed a spindle-shaped, myofibroblast-like morphology, increased apoptosis, reduced adhesion, and enhanced production of EMT proteins such as fibronectin and type I collagen. The migration of lens epithelial cells under PMMA and silicone IOLs was substantial in the in vitro assay. This report demonstrates that hydrophobic acrylic lenses are more capsular biocompatible than PMMA and silicone lenses. The in vitro assays are reliable measurements for evaluating the responses of human lens epithelial cells to different IOL materials, and could advance our understanding of the preferential capsular opacification conferred by different IOL materials.