Risk factors for graft failure after penetrating keratoplasty were investigated in 961 patients from records collected prospectively by the Australian Corneal Graft Registry. The most common cause of graft failure was irreversible rejection. A multivariate proportional hazards regression analysis indicated that the key predictors of graft failure were: an indication for graft other than keratoconus or corneal dystrophy; a failed previous graft (ipsilateral eye); aphakia; inflammation at the time of graft; presence of an anterior chamber or iris-clip intraocular lens; graft size outside the range of 7.0 to 7.9 mm diameter; and corneal vascularization occurring in the postoperative period.