A prospective study was conducted of corneal endothelial damage associated with intraocular gas tamponade during pars plana vitrectomy performed in 44 patients. In addition to vitrectomy or combined vitrectomy-lensectomy, 25 patients (the gas-treated group) underwent intraocular gas tamponade, which was not performed in 19 patients (the control group). The central corneal endothelium was examined with a specular microscope preoperatively and 3 months postoperatively. Endothelial changes were quantitated by computerized morphometric analysis of individual cells. A total of 20 eyes were phakic after vitrectomy, 13 eyes in the gas-treated group and 7 eyes in the control group. The mean endothelial cell loss for the gas-treated group (1.9%) did not differ significantly from that for the control group (1.8%). Twenty-four eyes were aphakic after vitrectomy, 12 eyes in the gas-treated group and 12 eyes in the control group. The gas-treated group had a significantly greater cell loss (28.3%) than those in the control group (16.3%).