Methotrexate (MTX) is an antineoplastic antimetabolite with immunosuppressant properties. Folate antagonism is known to contribute to the antiproliferative effects of MTX, and release of adenosine from cells and inhibition of polyamines may explain its anti-inflammatory effects. These activities contribute to complex and multifaceted mechanisms that may make this drug an effective treatment for inflammatory and proliferative disorders. In this study the authors evaluate the effects of repeated injections of intra silicon oil (SO), methotrexate on the outcome of surgery for rhegmatogenous retinal detachment with Grade C proliferative vitreoretinopathy (C PVR). Eleven eyes of 11 patients (one woman, 10 men; mean age, 52.73±18.01 years [range, 18-80 years]) were included in this study. The follow-up period was 9±3 months (range, six to 15 months). Three eyes were phakic and remaining pseudophakic. Total retinal detachment with anterior and / or posterior C PVR was present in all eyes before surgery. Mean preoperative best-corrected visual acuity (BCVA) was 2.62±0.04 logMAR. All operated eyes exhibited retinal reattachment posterior to the equator during the follow-up period. Mean postoperative BCVA was significantly improved to 1.02±0.51 logMAR (p=0.003). Retinal reattachment was achieved in all eyes after surgery. Localised peripheral retinal re-detachment occurred in two eyes; however, the subretinal fluid was confined using laser photocoagulation spots, and both eyes exhibited stable retinal reattachment posterior to the equator during the follow-up period. None of the operated eyes developed posterior membrane or macular pucker. No other ocular or systemic adverse effects secondary to intra-SO injection of MTX were observed. Limitations: Small cohort. Short follow-up period.