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To evaluate and compare the effect of silicone oil and gas on the thickness of all retinal layers in eyes with macula-on retinal detachment (RD).Three hundred and sixty-seven eyes of 367 patients who received silicone oil tamponade and 310 eyes of 310 patients who received gas tamponade for the treatment of rhegmatogenous RD were initially reviewed. Automated retinal segmentation method using Spectralis optical coherence tomography was used for analysis. The primary outcome measure was the change in thickness of each retinal layer in the central 1 mm zone (silicone oil vs. gas tamponade). The secondary outcome measure was best-corrected visual acuity at postoperative 6 months and 9 months after primary RD surgery.Eyes in the silicone oil group (n = 33) had a statistically significant decrease in total retinal thickness of 23.61 + 17.01 μm and in the thickness of all retinal layers, except for photoreceptor layer at 6 months after primary RD surgery (P < 0.001). In the gas group (n = 31), the postoperative change in total retinal thickness was only 0.14 ± 7.26 μm (P = 0.93), with no significant decrease in any of the individual retinal layers. Postoperatively, the best-corrected visual acuity in the silicone oil groups was significantly worse than that in the gas group at 6 months and 9 months after RD surgery (P = 0.003 and P = 0.004, respectively). The postoperative decrease of the ganglion cell layer, outer plexiform layer, and outer nuclear layer thicknesses showed significant correlation with best-corrected visual acuity in the silicone oil group (all P < 0.05).Silicone oil tamponade had a significant impact on the reduction of retinal thickness and that the reduction of ganglion cell layer, outer plexiform layer, and outer nuclear layer thicknesses showed the strongest correlation with worse visual acuity outcome.