Purpose: To assess the effects of weekly post-operative intravitreal methotrexate injections on eyes with grade C proliferative vitreoretinopathy (PVR) that underwent surgical repair. Methods: Retrospective case–control study of 16 eyes with retinal detachment and grade C PVR. Seven eyes received weekly intravitreal MTX injections post-operatively as an adjunct and 9 eyes served as the control. The main outcome measure was the retinal re-attachment rate. Results: In the MTX group, 86% (6/7) of eyes had a complete retinal re-attachment at the end of the follow-up period. In contrast in the no MTX group, only 22.2% (2/9) of eyes had a complete retinal re-attachment (p = 0.0406). The patients in the MTX group received a mean of 6 injections (range 4–8). There were no cases of corneal epitheliopathy. Conclusions: Serial intravitreal MTX as an adjunct to surgical repair holds promise for the management of PVR. [Figure not available: see fulltext.]