To determine the efficacy of a combination of 5- fluorouracil and low- molecular- weight heparin (LMWH) to improve the outcome of surgery for established proliferative vitreoretinopathy (PVR). Double- masked, prospective, randomized, placebocontrolled clinical trial. Three tertiary- referral teaching hospital vitreoretinal surgical units. One hundred fifty- seven patients with established PVR (grade C, anterior or posterior) undergoing vitrectomy surgery. All patients underwent vitreoretinal surgery and silicone oil exchange with or without membrane peeling and/or retinectomy. Patients were randomly allocated to perioperative infusion with or without 5- fluorouracil (200 μ g/ml) and LMWH (5 IU/ml) in Hartmann’ s solution for 1 hour. The primary outcome measure was defined as posterior retinal reattachment after removal of silicone oil without any reoperations at 6 months. Secondary outcome measures recorded were posterior retinal reattachment, localized/tractional retinal detachment, visual acuity, macular pucker, hypotony, glaucoma, keratopathy, and cataract. Removal of silicone oil and reoperations were also recorded. Overall, at 6 months 84% of patients had full retinal reattachment and 94% had stable posterior retinal reattachment. There was no significant difference in success in the primary outcome measure (56% , treatment group; 51% , placebo group; P=0.59) or in secondary outcome measures or rates of complications. Secondary macular pucker occurred less often in the treatment group (6% vs. 17% at 6 months, P=0.068). A perioperative infusion of combined 5- fluorouracil and LMWH does not significantly increase the success rate of vitreoretinal surgery for established PVR. To determine the efficacy of a combination of 5-fluorouracil and low-molecular-weight heparin (LMWH) to improve the outcome of surgery for established proliferative vitreoretinopathy (PVR). Double-masked, prospective, randomized, placebocontrolled clinical trial. Three- referral teaching hospital vitreoretinal surgical units. One hundred fifty-seven patients with established PVR (grade C, anterior or posterior) undergoing vitrectomy surgery. All patients underwent vitreoretinal surgery and silicone oil exchange with or without membrane peeling and / or retinectomy. Patients were randomly allocated to perioperative infusion with or without 5-fluorouracil (200 μg / ml) and LMWH (5 IU / ml) in Hartmann’s solution for 1 hour. The primary outcome measure was defined as posterior retinal reattachment after removal of silicone oil without any reoperations at 6 months. Secondary outcome measures recorded were posterior retinal reattachment, localized / tractional retinal detachment Removal of silicone oil and reoperations were also recorded. Overall, at 6 months 84% ​​of patients had full retinal reattachment and 94% had stable posterior retinal reattachment. There was no significant difference in the rate of visual acuity, macular pucker, hypotony, glaucoma, keratopathy, and cataract. no significant difference in success in the primary outcome measure (56%, treatment group; 51%, placebo group; P = 0.59) or in secondary outcome measures or rates of complications. Secondary macular pucker occurred less often in the treatment group (6% vs. 17% at 6 months, P = 0.068). A perioperative infusion of combined 5-fluorouracil and LMWH does not significantly increase the success rate of vitreoretinal surgery for PVR.