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Purpose: To investigate the effects of vitrectomy (Vy) with or without same time cataract surgery and membrane plus internal limiting membrane peeling (MP+ILMP) on retinal oxygenation and choroidal volume and their role on postoperative outcome. Methods: Thirty‐two eyes were included in this prospective clinical study. All patients received 23 gauge Vy+MP+ILMP without endotamponade. Additional cataract surgery was performed in 14 patients. Follow‐up visits were scheduled at day 1, week 1, month 1 and month 3. At each visit, best corrected visual acuity (BCVA) using ETDRS charts (except at day 1), oxygenation of retinal vessels using the Oxymap T1, and optical coherence tomography (OCT, Heidelberg Spectralis) was performed. Results: Mean BCVA increased significantly from 73 ± 11 letters to 77 ± 7 letters at month 3 (p = 0.02). Mean central retinal thickness (CRT) decreased from 456 ± 84 µm at baseline to 418±58µm (p = 0.01 baseline versus month 3). In the cataract surgery group, CRT was higher at month 3 than in the group without (400 ± 58 µm versus 441 ± 51 µm; p = 0.007). There was no statistically significant difference in choroidal volume or oxygenation of retinal vessels between groups (additional cataract surgery versus vitrectomy alone). Oxygenation of retinal arteries tended to decrease at day 1 followed by an increase, but the changes did not reach the level of significance (p = 0.29 baseline versus month 3). Oxygenation of retinal veins increased significantly (p = 0.02 baseline versus month 1; p = 0.04 baseline versus month 3, accordingly). There was a significant negative correlation (Spearman correlation coefficient rs = −0.35, p = 0.047) between visual acuity and oxygenation of retinal veins at month 3. No statistically significant correlation was found between CRT and oxygenation of neither retinal arteries nor veins. Choroidal volume (CV) of the central mm did not change significantly during the study period (baseline: 0.203 ± 0.04 mm3, median: 0.206, month 3: 0.205 ± 0.04 mm3, p = 0.54). There was no statistically significant effect of choroidal volume at baseline on postoperative clinical outcomes (change in BCVA estimate [95% CI]: 7 [−76; 90], p = 0.86; change in CRT: 147 [−577; 871], p = 0.68). Conclusion: Oxygen saturation may affect the visual acuity outcome but not the CRT in patients after vitrectomy for epiretinal membrane. Choroidal thickness had no statistically significant influence on the study outcomes. Further studies are needed to evaluate if the measurement of retinal oxygenation may be helpful in the decision for surgery. [ABSTRACT FROM AUTHOR]