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To evaluate the outcomes and complications of surgical management with 25-gauge pars plana vitrectomy (PPV) and silicone oil (SO) tamponade in complex vitreoretinal diseases.Retrospective review of a consecutive, interventional case series at a single center.Thirty-five eyes of 35 patients were included in the study. The indications for vitrectomy included tractional retinal detachment (11 eyes), macular hole (6 eyes), proliferative vitreoretinopathy or recurrent retinal detachment (9 eyes), neovascular glaucoma (3 eyes), giant retinal tear (3 eyes), and pathologic myopia with epiretinal membrane or macular hole (3 eyes). All patients underwent 25-gauge PPV with either 1,000-centistoke (n = 31) or 5,000-centistoke (n = 4) SO tamponade infused through a 24-gauge angiocatheter. No intraoperative complications were noted. The median preoperative visual acuity was counting fingers (range, 20/50 to light perception). The median postoperative visual acuity after a median follow-up of 6 months (range, 1–19 months) was 20/200 (range, 20/30 to light perception). A small subconjunctival SO bleb was identified in two patients. Recurrent retinal detachment occurred in three patients. No significant complications relating to the use of SO in the setting of 25-gauge PPV occurred.Advances in 25-gauge PPV instrumentation have enabled expanding indications for 25-gauge PPV. 25-Gauge PPV with SO tamponade is safe and efficient and can be considered in the surgical management of complex vitreoretinal disease.