Purpose: To evaluate the risk factors of corneal GRAFT REJECTION and failure in cases of penetrating keratoplasty (PK) performed during the years 1998-1999.Materials and Method: As a cross sectional study, demographic and individual characteristics, causes of PK, REJECTION types, and risk factors were evaluated. Risk factors of GRAFT REJECTION, survival, duration of clarity, and finally failure rates for each factor were studied. Data was analyzed with SPSS 10.0; Chi- square and multivariate regression tests were used for statistical analysis.Result: During two years of study, 295 PKs were performed on 286 patients including 67% men. Average age was 37 ± 20 years. Patients were followed for 20 ± 10 months. GRAFT REJECTION occurred in 31.8% of cases within 7.3 ± 6 month. Endothelial REJECTION was the most common type of REJECTION (20.7%). Risk factors for REJECTION were: extensive corneal vascularization, reGRAFT, iridocorneal adhesions, irritating suture, active intraocular inflammation at the time of operation, secondary anterior segment surgery, history of trauma, poorly controlled intraocular pressure (IOP) and glaucoma, previous GRAFT REJECTION, reactivation of herpes on the GRAFT, and eccentric PK (P<0.05). On the other hand, patients' age at the time of PK, donor cornea size, and bilateral PK were not found to be a significant risk factor for GRAFT REJECTION (P>0.05).Conclusion: Severity and extent of recipient corneal vascualrization, iridocorneal adhesions, irritating sutures, active inflammation, reGRAFT, trauma, poorly controlled IOP, recurrence of herpetic keratitis, eccentric GRAFT, and GRAFT ulcer were related to GRAFT REJECTION. Recognition of these risk factors and early diagnosis and proper treatment of GRAFT REJECTION can extend GRAFT survival and clarity.