<h3>Objective:</h3> To determine whether hospital-ascertained atrial fibrillation (AF) is associated with subsequent central retinal artery occlusion (CRAO). <h3>Background:</h3> Atrial fibrillation is a major risk factor for cerebral ischemic stroke. However, it is not known whether AF predicts the development of central retinal artery occlusion. <h3>Design/Methods:</h3> A retrospective cohort study was undertaken using data from the California Healthcare Cost and Utilization Project (HCUP) State Inpatient and State Emergency Department Datasets (SID/SEDDs). Patients 18 years and older discharged from non-federal hospitals between 2005 and 2011 who did not have a history of CRAO were analyzed. AF and CRAO were identified using validated ICD-9-CM diagnosis codes. Association between AF and CRAO was modeled using a Fine-Gray method with death as a competing risk with adjustment for age, biological sex, race, and vascular comorbidities. <h3>Results:</h3> A total of 12,181,778 patients were included, 806,397 with AF and 11,375,381 without AF. In total, 309 patients had CRAO. In an unadjusted analysis, there was a higher risk of CRAO in patients with versus without AF (HR 2.24 (95% CI: 1.51 to 3.32)). After adjustment for pre-specified covariates, there appeared to be a lower hazard of CRAO in patients with AF (aHR 0.61 (95% CI: 0.45 to 0.98)). Further analyses including cerebral ischemic stroke (aHR 1.16 (95% CI: 1.14 to 1.18)) and specifically embolic stroke (aHR 4.29 (95% CI 4.10–4.48)) as positive controls argued against overadjustment bias. We present sensitivity analyses including CRAO identified in any position of the ICD list, using different ascertainment windows for AF and using broader categories of retinal ischemia. <h3>Conclusions:</h3> The incidence of CRAO was higher in patients with AF than those without AF, but the hazard of CRAO was not higher for patients with AF after adjustment for measured covariates. Endpoint and exposure ascertainment may have been limited by inclusion only of inpatient and emergency department encounters. <b>Disclosure:</b> Mr. Lusk has received research support from American Heart Association. The institution of Ms. Song has received research support from Research to Prevent Blindness. Ms. Unnithan has nothing to disclose. Dr. Al-Khalidi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medpace. Dr. Al-Khalidi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring . The institution of Dr. Al-Khalidi has received research support from NIH/NHLBI. Jonathan Piccini has nothing to disclose. Dr. Xian has nothing to disclose. Dr. O’Brien has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boehringer Ingelheim. The institution of Dr. O’Brien has received research support from Pfizer. The institution of Dr. O’Brien has received research support from BMS. Dr. Mac Grory has nothing to disclose.