Purpose: This work evaluates the effect of antiplatelet and anticoagulant agents on clinical outcomes, optical coherence tomography (OCT) parameters, and macular ischemia in eyes with central retinal vein occlusion (CRVO). Methods: A retrospective longitudinal cohort study was performed to evaluate patients with CRVO. Demographics, OCT parameters before and after treatment, macular ischemia on fluorescein angiography, and clinical outcomes including the number of injections received were analyzed. Results: A total of 365 patients with CRVO were identified. The average follow-up was 36 months. Antiplatelet or anticoagulant agent use was not associated with a significant difference in visual acuity (VA), prevalence of macular edema, or central subfield thickness on OCT at presentation or final visit. The use of 81-mg aspirin alone was associated with an increased prevalence of foveal hemorrhage at presentation. Patients who were taking an antiplatelet agent, an anticoagulation agent, or both and had an ischemic CRVO with logMAR VA of less than 1.0 experienced improved VA at the final study visit. Patients given antiplatelet or anticoagulant agents had a similar incidence of neovascular sequelae compared with patients not administered these agents. Conclusions: In eyes with CRVO, the use of antiplatelet or anticoagulant agents at CRVO onset was not associated with significantly different functional outcomes, except in ischemic CRVO eyes with VA of less than 20/200. The use of 81-mg aspirin was associated with foveal hemorrhage at CRVO presentation. Otherwise, the use of any antiplatelet agent or anticoagulation was not associated with any CRVO structural outcomes.