OBJECTIVE To evaluate the effect of silicone oil (SO) on the corneal endothelium in SO filled phakic and pseudophakic vitrectomizied eyes. METHODS This prospective comparative consecutive case-control study evaluated the corneal endothelial characteristics of 64 SO filled vitrectomizied eyes (case group) as compared to 46 vitrectomizied eyes without SO injection (control group). Endothelial cell densities (ECD), coefficient of variation (CV), and percentage of hexagonal cells (hexagonality) at the corneal center were evaluated preoperatively, 1 month and 6 months after surgery using noncontact specular microscopy and were compared between the two groups. Exclusion criteria were previous vitreoretinal surgery, aphakia, any degree of anterior chamber inflammation, SO bubbles in the anterior chamber and increased intraocular pressure in the postoperative period. RESULTS Six months after SO injection, mean ECD was 2,438.2±327.6 cell/mm(2) in the case group and 2,462.6±361.7 cell/mm(2) in the control group (P = 0.714) and mean hexagonality was 49.6 ± 6.8 and 54.6 ± 8.9, in the case and control groups, respectively (P = 0.004). Six months after operation, CV in the case group was 39.3 ± 5.6 and that in the control group was 35.7 ± 6.4 (P = 0.003). CONCLUSIONS Although the presence of SO in the vitreous cavity of phakic and pseudophakic eyes causes slight reduction in the number of endothelial cells, however it leads to significant changes in endothelial cell morphology. Thus, removal of SO after reaching the desired tamponade effect is recommended.