Purpose: To compare the Alcon AcrySof® Natural (SN60AT) and AcrySof (SA60AT), the AMO Sensar® (AR40e) and ClariFlex®, and the Pfizer CeeOn® Edge 911A intraocular lenses (IOLs) as to their ability to protect retinal pigment epithelial (RPE) cells from light damage mediated by the lipofuscin fluorophore A2E. Setting: Department of Ophthalmology, Columbia University, New York, New York, USA. Methods: Cultured human RPE cells (ARPE-19 cell line) that had accumulated A2E were exposed to blue (430 nm ± 30), green (550 ± 10 nm), or white (390 to 750 nm) light with and without an IOL in the light path. Results: The blue light-absorbing AcrySof Natural IOL was associated with significant reduction (78% to 82%; P<.01) in the death of A2E-laden RPE that were exposed to blue, white, and green light. The decrease in the incidence of cell death was greater in magnitude than would be expected from the amount of light that was absorbed by the IOL. The considerably smaller declines in cell death observed with the AcrySof, Sensar, ClariFlex, and CeeOn Edge IOLs were likely due to nonspecific reductions in light transmittance. Conclusions: By absorbing blue light, the AcrySof Natural IOL shields RPE cells that have accumulated the aging lipofuscin fluorophore A2E from the damaging effects of light. A long-term population-based clinical trial would determine whether a blue light-absorbing IOL can reduce the risk for or progression of age-related macular degeneration.