PURPOSE: To quantify the burden of illness for incident branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in a commercially insured working-age (commercial) and Medicare US population. METHODS: Retrospective cohort analysis of health care claims from 2003 through 2008 from commercial and Medicare patients with ≥2 outpatient diagnoses for BRVO or CRVO. The index date was the first retinal vein occlusion diagnosis. Patients with medical and pharmacy benefits were followed ≥1 year preindex and then between 1 year and 3 years postindex. Incidence and prevalence of retinal vein occlusion was determined. Burden of illness was compared with matched control subjects without retinal vein occlusion. RESULTS: The commercial sample comprised 1,188 CRVO and 2,252 BRVO cases, whereas the Medicare sample had 2,739 CRVO and 4,573 BRVO cases. Adjusted ratio of case-to-control, all-cause expenditures for commercial patients at 1 year and 3 years postindex were 1.88 and 1.68, respectively, for BRVO and 1.42 and 1.36, respectively, for CRVO. For Medicare patients, these were 1.29 and 1.13, respectively, for BRVO and 1.23 and 1.14, respectively, for CRVO. All comparisons were significant (P < 0.001). CONCLUSION: Health care utilization and expenditures for commercially insured working-age and Medicare patients with BRVO or CRVO were significantly greater than those for control subjects. Retinal vein occlusion development may be a marker for the increased severity of systemic vascular disease.