SummaryNon-arteritic anterior ischaemic optic neuropathy (NAION) is caused by ischaemia of the optic nerve head. The pathophysiology of NAION is unclear, and no proven effective treatment exists. Patients, methods: We analyzed thrombophilic risk factors and determinants of atherosclerosis and inflammation in 109 consecutive patients and 109 age- and sex-matched volunteers using a case-control design. Results: High levels of fibrinogen (>384 mg/dl; OR 3.2, p = 0.003), factors VIII:C (>183%; OR 2.6, p = 0.02), IX (>153%; OR 2.6, p = 0.026), XI (>142%; OR 3.4, p = 0.006), von Willebrand factor (activity >205%; OR 3.1, p = 0.005; antigen >194%; OR 3.5, p = 0.002), and triglycerides (>228 mg/dl; OR 2.8, p = 0.026), higher platelet counts (>294 000/[uni03BC]l; OR 2.5, p = 0.04), low levels of HDL cholesterol (<40 mg/dl; OR 2.7, p = 0.032), and an accelerated erythrocyte sedimentation rate (>20 mm/h; OR 4.4, p = 0.003) were associated with NAION. Conclusion: Our findings support the contention of a complex pathogenesis of NAION resulting from the coincidence of proatherogenic, prothrombotic and proinflammatory processes. The alterations described could be causative, side effects, or just coincidental findings.