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PURPOSE To compare the impact of surgical timing on anatomical and functional outcomes of vitrectomy for open-globe injury. METHODS Fifty-three patients were entered into this prospective open-label study, with 26 patients randomized into early surgery group (vitrectomy conducted within 4 days) and 27 into delayed surgery group (vitrectomy performed between 10-14 days after injury). Six-month data were available for 46 patients and 7 were lost to follow-up. The main outcome measures were incidence of traumatic proliferative vitreoretinopathy assessed intraoperatively and postoperatively, reattachment of retina, eye enucleation, improvement of the best-corrected visual acuity, and complications. RESULTS Patient demographics and surgical intervention were similar in both groups. Final analysis of 46 patients demonstrated higher rates of traumatic proliferative vitreoretinopathy assessed both intraoperatively and postoperatively in the delayed group (P = 0.000; P = 0.054). In the early surgery group, 18 of 21 patients had retinal detachment, of which 15 patients (83%) achieved retinal reattachment by the first vitreoretinal surgery, 2 patients (11%) by a second surgery, and 1 (6%) received enucleation. In the delayed surgery group, 22 of 25 patients had retinal detachment. Retinal reattachment was achieved in 7 (32%) and 8 (36%) with the first and the second surgery, respectively, and 7 patients (32%) received enucleation (P = 0.005). In the early surgery group, best-corrected visual acuity improved significantly, moderately, and decreased in 8 patients (38%), 11 eyes (52%) and 2 eyes (10%), respectively. In the delayed surgery group, best-corrected visual acuity improved significantly, moderately, and worsened in 3 eyes (12%), 12 eyes (48%), and 10 eyes (40%) (P = 0.041), respectively. No statistically significant difference was observed in the rate of postoperative complications between the two groups. CONCLUSION Early vitrectomy after open-globe injury leads to better anatomical and functional outcomes.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.