OBJECTIVE: To investigate correlation of levels of plasma D-dimer, fibrinogen, and homocysteine (Hcy) with migraine. STUDY DESIGN: This is a case-control study. A total of 268 migraine patients who presented at the Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, from September 2016 to January 2021 were selected as the migraine group, while 150 healthy individuals during the same period were selected as the control group. They underwent medical history and demographic data collection as well as comprehensive neurological physical examination, and they all received various biochemical indexes measurement. Multi-factor logistic regression and ROC curve area analysis were applied to determine the correlation between levels of plasma D-dimer, fibrinogen, Hcy, and migraine by comparing the general clinical data and the blood biochemical parameters between the 2 groups. RESULTS: The levels of plasma D-dimer, fibrinogen, and Hcy were higher in the migraine group than those in the control group (p<0.05). Multi-factor logistic regression analysis revealed elevated levels of plasma D-dimer, fibrinogen, and Hcy as risk factors for migraine. ROC curve analysis showed that the area under the curve for the prediction of migraine by plasma D-dimer was 0.711 (95% CI 0.661~0.761, p<0.05), with a sensitivity of 80%, specificity of 55%, and optimal diagnostic value of 0.255 µg/mL. The area under the curve for the prediction of migraine by fibrinogen was 0.764 (95% CI 0.716–0.811, p<0.05), with a sensitivity of 65%, specificity of 85%, and optimal diagnostic value of 4.295 g/L. CONCLUSION: Elevated levels of plasma D-dimer, fibrinogen, and Hcy are independent risk factors for migraine. Plasma levels of D-dimer and fibrinogen are predictive of migraine. In general, levels of plasma D-dimer, fibrinogen, and Hcy may be biomarkers of migraine. © Science Printers and Publishers, Inc.