<i>Purpose:</i> The aim of the study was to investigate the plasma homocysteine levels in patients with retinal vein occlusion (RVO) in order to reveal whether hyperhomocysteinemia was a risk factor for RVO. <i>Methods:</i> Thirty-three consecutive patients diagnosed to have RVO of any type and 25 age- and sex-matched controls without RVO were included in this prospective case-control study. Data regarding age, sex, history of hypertension, diabetes mellitus, other vascular events, glaucoma, medications and smoking habits were obtained from all subjects. Several laboratory tests relating to vascular disease including cholesterol, triglyceride and hematocrit were checked. The plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography (normal range: 5–15 µmol/l). Plasma folate, vitamin B₁₂ and creatinine levels were also studied since these vitamins and impairment of renal function might affect plasma tHcy values. <i>Results:</i> Patients with RVO had a significantly higher tHcy level (median: 11.7 µmol/l, range: 7.2–25 µmol/l) compared to controls (median: 10.3 µmol/l, range: 6.7–13.4 µmol/l; p = 0.005). Nine of 33 patients with RVO (27.3%) had an elevated plasma tHcy level, whereas none of the controls had an abnormal tHcy value (p = 0.004). Plasma folate, vitamin B₁₂ and creatinine levels were comparable between the two groups (p > 0.05). <i>Conclusions:</i> The present study suggests an association between hyperhomocysteinemia and RVO. Further controlled studies with a large number of cases are needed to investigate the exact role of hyperhomocysteinemia in RVO.