Purpose. To compare endothelial damage induced by different cataract incision sites and sizes using specular microscopy. Setting. Department of Ophthalmology, Hospital of San Dona di Piave, Venice, Italy. Methods: Eighty-one eyes having phacoemulsification were randomly assigned to 1 of 3 groups of 27 eyes each: 3.5 mm clear corneal incision (CCl) with silicone foldable intraocular lens (IOL) implantation; 5.5 mm sutured CCl with poly(methyl methacrylate) (PMMA) IOL implantation; 5.5 mm scleral tunnel with PMMA IOL implantation. All incisions were centered at the 120-degree semimeridian; that is, they were superotemporal in right eyes and superonasal in left eyes. Noncontact specular microscopy was performed in the center and at the 12 o'clock position preoperatively as well as 1 week and 1, 3, and 12 months postoperatively, The endothelial cell density, mean cell area, cell size variation coefficient, percentage of hexagonality, and corneal thickness were considered. Results: Progressive endothelial cell loss and an increase in mean cell area occurred in all groups during the follow-up. The cell loss percentages relative to the endothelial center appeared similar among the groups and slightly although not significantly lower in the scleral tunnel group, The scleral tunnel group had a statistically significant lower cell loss percentage at the 12 o'clock position than the 2 CCl groups at all follow-ups. Conclusions. The scleral tunnel group had less postoperative endothelial damage than the 2 CCl groups, with a statistically significant difference at the 12 o'clock position. This is probably because the scleral tunnel incision is placed more posteriorly and therefore induces less direct and indirect endothelial trauma. J Cataract Refract Surg 2002; 28: 118-125 (C) 2002 ASCRS and ESCRS.