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Background: Early vitrectomy for postsurgical endophthalmitis may improve visual acuity outcomes. Silicone oil as a tamponade has some potential benefits in the management of endophthalmitis. This study aims to evaluate the use of a silicone oil tamponade in the surgical management of endophthalmitis. Material and Methods: All patients with a pars plana vitrectomy with silicone oil tamponade for postsurgical endophthalmitis at the Department of Ophthalmology, University of Bonn, Germany, between 2017 and 2021 were retrospectively reviewed. We included all preoperative data, including BCVA at diagnosis, clinical findings, and symptoms. For every follow-up visit, we looked at BCVA and complications. Results: In total, 82 patients were included in this study. The mean follow-up was 13.1 months (range 1–58 months). An intravitreal injection was the cause in 42 patients (51.2%) and cataract surgery in 29 patients (35.4%). The mean interval between the causing event and the date of onset was 8.8 days (range, 1–59 days). The most prevalent pathogen was Staphylococcus epidermidis in 16 patients (19.5%). In 47 patients (57.3%), no pathogen was found. The initial best-corrected visual acuity was 2.1 logMAR and improved significantly to 1.0 logMAR after six months (p < 0.001) and 1.1 logMAR after 1 year (p < 0.001). In a multivariate analysis, a low BCVA at diagnosis (p = 0.041) was a significant predictor for poor visual acuity outcomes. A total of 17 patients (20.1%) developed postoperative complications. Five patients (6.1%) needed an anterior chamber washout with repeated injections of antibiotics. Two patients (2.4%) had persistent fibrin and were treated with YAG-laser treatment. Three patients (6.7%) developed a retinal detachment. Two patients (2.4%) had persistent corneal decompensation with endothelial cell loss and received perforating keratoplasty. We performed a matched-pair analysis (n = 30, each group n = 15) to compare a silicone oil tamponade with BSS at the end of surgery. The visual acuity outcome showed no significant differences (BCVA after one year: 1.17 logMAR in eyes with silicone oil and 0.90 logMAR in eyes with BSS; p = 0.684). Conclusions: In our study, a vitrectomy with silicone oil tamponade in the surgical management of postoperative endophthalmitis led to a significant improvement in visual acuity and had a low complication rate. Low BCVA at diagnosis was significantly associated with poor visual acuity outcomes. A comparison of silicone oil and BSS at the end of surgery showed similar results. [ABSTRACT FROM AUTHOR]