Purpose To evaluate the effect of combined subconjunctival and topical bevacizumab treatment on corneal graft survival rate in high-risk eyes. Methods Prospective, consecutive, interventional case series. Fifty eyes of 50 high-risk patients scheduled for penetrating keratoplasty (PK) were included in the study; two Stevens–Johnson syndromes (SJS), five corneal combustions due to chemical burn, seven post-traumatic vascularised leucomas, 11 post-infectious vascularised leucomas, 19 rejected grafts and six corneal ulcers. Additional surgeries such as autologous limbal stem cell and/or amniotic membrane transplantation were performed together with PK in ten cases. All eyes received subconjunctival injection of 0.5 ml bevacizumab (25 mg/ml) after PK. Eyes with more than two quadrants of neovascularisation (NV) received bevacizumab drops (25 mg/ml) postoperatively for up to 12 weeks. Donor grafts were followed up for best-corrected visual acuity, graft clarity, change in NV, endothelial cell density loss (ECD), and adverse events. Mean follow-up was 36.5 months (range 32–61). Results Best-corrected visual acuity increase was statistically significant in 82 % (41/50) of eyes 3 years after PK (paired t -test, p  = 0.02). Thirty-five (70 %) high-risk grafts remained clear throughout the 3-year follow-up period. Decrease of corneal NV was observed in 84 % (42/50) of eyes treated with bevacizumab. ECD changed from preoperative 2,864 ± 301 down to 1,905 ± 187 cells/mm 2 at 3 postoperative years. A non-healing epithelial defect was recorded in one patient with SJS after 12 weeks of topical bevacizumab. Conclusion Combined subconjunctival and topical bevacizumab treatment may improve corneal graft survival rate in the majority of high-risk cases.