Background and Objective: Objective of this study was to identify the risk factors for corneal graft failure and isolate microrganisms associated with graft infections after penetrating keratoplasty . The present study was conducted in the Department of Ophthalmology at tertiary care centre in central India. Methods: The present study was a case control study conducted in the Department of Ophthalmology at tertiary eye care from November 2018 to October 2020. Patients operated for optical penetrating keratoplasty attending eye OPD were examined. Results: Preoperative risk factors- adjusted risk associated with donor’s age > 60 years was 8.798 with p-value 0.001, indicating significantly higher risk of graft failure as compared to donor’s age < 60 years. Presence of corneal vascularity had a significantly increased adjusted risk i.e. 7.542 with a p-value 0.002, as compared to those without corneal vascularity . Perioperative risk factors: the graft size > 8.5mm has significantly higher adjusted risk of graft failure with estimate of 15.296 with a p-value of 0.013, as compared to the reference category 8.0 – 8.5mm. Postoperative risk factors: The presence of raised IOP had significantly higher adjusted risk of graft failure with estimate 10.26 with a p-value 0.011, as compared to those with normal IOP. Adjusted risk estimate corresponding to epithelial defects was 8.464 with a p-value 0.014, suggesting increased risk as compared to those without the defect. The likelihood of graft failure corresponding to graft rejection was also significantly higher as indicated by adjusted estimate of 5.688 (95% CI: 1.048 – 30.869) with a p-value 0.044, compared to those with no graft rejection. Interpretation and conclusion: Pre-operative risk factors for graft failure: 2 or more quadrant corneal vascularisation, peripheral anterior synechiae and older donor age (>60 years). Peri-operative risk factors: repeat keratoplasty and larger donor graft size >8.5mm. Post operative risk factors: elevated IOP, suture problem, epithelial defect, graft rejection, post penetrating keratoplasty infection were postoperative risk factors for graft failure. As per multiple logistic regression Pre-operative risk factors were Corneal vascularization and Donor age of >60 years Peri-operative risk factors were Graft size of >8.5mm Post operative risk factors were raised IOP, epithelial defect, graft rejection. Although other factors indicated increased risk in univariate analysis, evidence was statistically insignificant in multivariate analysis.