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PURPOSE To assess the optimal interval of preoperative intravitreal bevacizumab (IVB) administration in diabetic subjects undergoing pars plana vitrectomy (PPV) for severe manifestations of active proliferative diabetic retinopathy (PDR). DESIGN Randomized clinical trial. METHODS One hundred and fifty-six patients with PDR-related complications requiring PPV were prospectively randomized into 1 of 2 treatment groups: Group A received IVB (2.5 mg/0.1 mL) 1-3 days before PPV, while Group B received IVB (2.5 mg/0.1 mL) 5-10 days before PPV. The primary outcome was best-corrected visual acuity (BCVA) at 6 months follow-up. Secondary outcome measures were intraoperative surgery time, intraoperative complications, postoperative complications, and incidence of unplanned PPV at 6 months follow-up. RESULTS One hundred and twenty-five subjects underwent PPV and completed the 6-month follow-up interval. Group B patients had better final BCVA (P = .033) and were less likely to have a postoperative complication (P = .018) when compared to Group A patients. The mean difference in final BCVA between groups was 0.22 logMAR (95% confidence interval: 0.02-0.43, P = .017). Group A was 3.90 (95% confidence interval: 1.08-17.31, P = .046) times more likely to have a loss of 1 or more logMAR lines of final BCVA when compared to Group B. There were no significant differences among the treatment groups with regard to baseline features, intraoperative surgery time, intraoperative complications, and incidence of unplanned PPV during the study interval. CONCLUSIONS This randomized clinical trial demonstrated better postoperative outcomes at 6 months when subjects received preoperative IVB 5-10 days before PPV compared to 1-3 days for the treatment of PDR-related complications.