Background Non-infectious endophthalmitis was reported to occur after cataract surgery or intravitreal injections. This study reported a series of patients having non-infectious endophthalmitis after pars plana vitrectomy in the same two operation rooms during the same period to estimate the risk factors for non-infectious endophthalmitis after vitrectomy. Methods Medical records of patients who presented with severe non-infectious endophthalmitis following vitrectomy between May 13 and June 8, 2011, were reviewed. The presenting symptoms and signs were collected, including visual acuity, intraocular pressure, cornea and anterior chamber activity. The treatments and results of microbiology examination were also recorded and analyzed. Results Ten patients were identified with severe non-infectious endophthalmitis, presenting 1 day after pars plana vitrectomy. Three eyes (30%) had previous intraocular surgeries, four (40%) had proliferative diabetic retinopathy, and one (10%) got pars plana vitrectomy combinded with phacoemulsification and intraocular lens implantation. All the patients were initially treated with topical and/or oral steroids. Only two patients had intravenous antibiotics because of the atypical presentation. One eye had paracentesis because of high intraocular pressure and the aqueous sample was sent for microbiological examination. The culture of the aqueous, air in the operation room, the swab from hand of surgeons, infusion fluid, and vitrectomy effluent were all negative for bacteria and fungi. The inflammation regressed rapidly after the initial treatment. Conclusions Intraocular surgery history, poor general health status, longer operation time, and more surgical procedures are the risk factors for non-infectious endophthalmitis after vitrectomy. It responds well to steroids.