BACKGROUND Penetrating keratoplasty (PK) remains the most common corneal transplant method in China. In this paper we aim to analyze the outcomes and the potential factors associated with graft failures of PKs in one of the largest keratoplasty centers in Eastern China during the past 4 years. MATERIAL AND METHODS A retrospective review was performed on 502 eyes from 481 recipients undergoing PKs from January 2018 to December 2021 at the Eye and ENT Hospital of Fudan University. Graft failures presenting between the first postoperative day and 8 weeks were defined as early graft failure and failures presenting between 8 weeks and the end of the 1-year follow-up as late failure. Cox proportional hazards regression models and logistic regression models were used to assess the association between factors and failures. RESULTS Of the 93 failed cases, 36 were classified as early failure and 57 as late failure. Risk factors, expressed as hazard ratio (HR) and confidence interval (CI), for the failures include the following: burns (HR: 12.56, 95% CI [2.4, 65.71]), nonsuppurative inflammation (HR: 11.06, 95% CI [2.49, 49.03]), suppurative inflammation (HR: 12.49, 95% CI [2.76, 56.37]), immune disease (HR: 1.70, 95% CI [0.64, 4.48]), low donor endothelial cell density (ECD) (HR: 0.92/100 cells, 95% CI [0.87, 0.98]), and surgical complications (HR: 1.83, 95% CI [1.06, 3.17]). Two social factors were strongly negatively associated with late failures: completion of compulsory education (HR: 0.45, 95% CI [0.21-0.94]) and marriage (HR: 0.27, 95% CI [0.09-0.81]). CONCLUSIONS Indications, surgical complications, immune disease of the recipient, and lower donor ECD were risk factors for failure. Social factors also affect the ocular health after PK in the long term.