Purpose: To examine the reoperation rate of amniotic membrane transplantation (AMT) and clarify the risk factors for AMT reoperation in severe ocular surface (OS) disorders (OSD). Study design: Retrospective cohort study. Participants: We reviewed the medical records of all AMT cases between April 1998 and June 2019 at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Methods: Primary diseases and AMT reoperation rates were examined. In severe OSD cases (Stevens–Johnson syndrome, ocular cicatricial pemphigoid, and chemical/thermal burns), preoperative OS Grading Score (OSGS), surgical procedures combined with AMT, and risk factors for reoperation were investigated and assessed. Results: Over a period of 21 years and 3 months, 750 AMTs were performed on 664 eyes of 594 cases. AMT was repeated on 51 of those 664 eyes (7.7%), and most frequently performed on 25 out of 196 eyes (12.8%) afflicted with severe OSDs. In severe OSDs, OSGS was significantly higher in the reoperation group compared to no-reoperation group (P<0.05), suggesting corneal epithelial defects, conjunctival hyperemia, trichiasis, mucocutaneous junction involvement, and corneal opacity as being risk factors for re-AMT (univariate analysis). In logistic regression analysis, only conjunctival hyperemia was a risk factor, with odds ratios (OR) of 2.65 (95%CI: 1.34–5.22, P=0.005). AMT combined with cultivated or donor corneal epithelial transplantation reduced reoperation risk with an OR of 0.92 and 0.63, respectively. Conclusions: In severe OSD cases, the effect of AMT is limited. Higher OSGSs, especially in conjunctival hyperemia, are associated with a high risk of repeat AMT. © The Author(s) 2025.