Pars plana vitrectomy (PPV) and silicone oil endotamponade have been used as a treatment in rhegmatogenous retinal detachment (RRD). Improvement in the modality of spectral-domain optical coherence tomography (SD-OCT) allows for the assessment of ganglion cell layer-inner plexiform layer (GCL-IPL) in the macular region. Information about the GCL-IPL status may be a response to the question as to why the visual recovery after PPV with silicone oil tamponade is incomplete. The aim of the study was to evaluate the impact of silicone oil on GCL-IPL and compare it with other endotamponade types such as Sulfur hexafluoride gas (SF6), Perfluoropropane gas (C3F8) used during PPV performed due to RRD. The study involved 57 eyes after PPV and 57 healthy, control eyes of patients with primary RRD who had undergone successful PPV. The patients were divided into three subgroups depending on the endotamponade type, and were tracked with complete ophthalmological examination during a period of 6 months. PPV with internal tamponade silicone oil, 24% SF6 or 14% C3F8 was performed. The medical records were reviewed and compared between the groups. SD-OCT analysis detected a significant reduction of average GCL-IPL thickness and reduction of GCLIPL parameter in almost all examined sectors in the group with silicone oil endotamponade during all follow-up visits (P<0.05). The study showed a significant vision deterioration in the silicone oil group in comparison with the SF6 group on all follow-up visits (P<0.05). This is the first in vivo SD-OCT study describing the toxic effect of silicone oil endotamponade on GCL-IPL complex after PPV for RRD. The study confirmed that the GCL-IPL complex value can be a predictive factor for assessing the final visual acuity. SD-OCT should be recommended as a clinical standard in the followup treatment of patients after PPV for RRD, especially with the use of silicone oil endotamponade. Plain Language Summary: The aim of the study was to examine the impact of silicone oil on the ganglion cell complex. The ganglion cell is a neuron type located in the retina and takes part in transmitting visual information from the retina to the brain. Silicone oil is a substance used during eye surgery called pars plana vitrectomy. This tamponade type acts to hold the retina in a proper position. However, during the retinal detachment, which is the separation of the retina from the layer underneath, a reduction of neurons is observed. We decided to use a new technology device called SD-OCT to determine the thickness of the ganglion cell complex. We compared the impact of silicone oil with other tamponade types. We found that silicone oil causes a reduction in the ganglion cell complex. Moreover, we observed vision deterioration in eyes treated with a silicone oil tamponade. The research describes the toxic effect of silicone oil on ganglion cells. Ganglion cell values may be used to determine visual improvement or deterioration after eye surgery with silicone oil tamponade. SD-OCT should be a clinical standard in monitoring patients with silicone oil tamponade.