Background: Over the past decade, Penetrating Keratoplasty (PKP) graft failure has been increasingly managed by Descemet Membrane Endothelial Keratoplasty (DMEK). Our aim is to emphasis the importance of preoperative evaluation by Anterior-Segment Optical Coherence Tomography (AS-OCT) and present the clinical outcomes and surgical modifications of DMEK performed for Secondary PKP graft failure.Methods: A retrospective medical records review of patients that underwent DMEK for failed PKP at Hadassah Medical Center in 2018-2019. Collected data included demographic characteristics, PKP graft size measured by AS-OCT, corneal donor endothelial cell density (ECD), intra-operative surgical method adjustments, post-operative complications, visual acuity in Snellen (VA), central pachymetry and post-operative ECD.Results: Included were 16 patients (9 males) and 16 eyes. The study period was 18 months. Mean age at performing DMEK was 63 years. Before DMEK, mean VA and central pachymetry were 0.04 and 685µm, respectively. At last follow up, they significantly improved to 0.3 (p-value=0.001) and 542µm (p-value=0.008) respectively. Mean ECD for donor grafts was 2662 cells per mm2. Post-operative ECD was available only for 7 cases with a mean of 1391 cells per mm2 (p-value=0.0002). At last follow up, 93.75% of the grafts were attached. Graft failure rate was 6.25% due to late decompensation, graft detachment rate and rebubbling rate were 18.75% respectively. Conclusion: A suitable case-based pre-operative evaluation by AS-OCT may play a vital role in DMEK for failed PKP. No less important is to take into consideration multiple surgical adjustments. Both may further decrease complications rates along with accelerating visual recovery.