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Purpose: To evaluate the efficacy of dexamethasone intravitreal implants (DEX implant) in patients with treatment-resistant macular edema (ME) owing to branch and central retinal vein occlusion (BRVO/CRVO), and the influence of prior vitrectomy on this treatment. Methods: Multicenter retrospective chart review was performed on 40 CRVO and 32 BRVO eyes with persistent ME despite intravitreal anti-vascular endothelial growth factor agents and/or intravitreal triamcinolone, and/or laser therapy. Each patient received ≥1 dexamethasone 700 μg implant between March 2011 and December 2015. Thirteen patients underwent prior vitrectomy. Data were collected on best-corrected visual acuity (BCVA), central macular thickness (CMT), time to relapse, and adverse events. Results: At the end of follow-up, BRVO eyes had a lesser CMT reduction from baseline compared to CRVO eyes (-122.50 ± 152.47 μm and -202.26 ± 194.09 μm, respectively). Neither BRVO nor CRVO eyes had a sustained BCVA benefit ( P  = 0.7041 and P  = 0.7027, respectively). Vitrectomized and nonvitrectomized eyes overall had a sustained significant CMT reduction throughout the study with -192.46 ± 172.62 μm and -164.02 ± 180.36 μm, respectively, at final follow-up. Similar time to relapse of 24.4 ± 6.5 and 23.3 ± 13.5 weeks, respectively, was observed. By the end of follow-up, BCVA had only improved in vitrectomized eyes. However, multivariable regression analyses showed no significant association between vitrectomy status and CMT or BCVA change after the first and last injection. Cataract formation and ocular hypertension occurred in 25% and 17%, respectively. Conclusions: Multiple DEX implant are effective in reducing CMT in patients resistant to previous treatments and appear to be similarly effective in vitrectomized and nonvitrectomized eyes.