Background: There is a reverse relationship between serum bilirubin level and incidence of stroke, heme oxygenase-1 (HO-1) can catalyze heme into bilirubin, it is unknown the association of HO-1 level with risk of stroke. Methods: Sixty patients with stroke and fifty patients with transient ischemic attack (TIA) were recruited. Serum level of HO-1, total and direct bilirubin, alanine transaminase, live function, lipid profile and infection status of patients were measured. Results: Significant differences were found between two groups in terms of serum levels of HO-1 (163.6 +/- 58.7 vs. 141.2 +/- 49.7, P=0.032), total bilirubin (10.1 +/- 4.6 vs. 15.8 +/- 2.7, P<0.001), direct bilirubin (3.2 +/- 2.1 vs. 5.9 +/- 1.2, P<0.001), fasting glucose (6.7 +/- 3.1 vs. 4.9 +/- 1.3, P<0.001), cholesterol (4.4 +/- 1.1 vs. 3.9 +/- 0.8, P=0.005) and diastolic blood pressure (DBP) (84.9 +/- 9.4 vs. 81.3 +/- 9.2, P=0.046). In multivariate analysis, serum direct bilirubin (OR, 2.83; P<0.001), total bilirubin (OR, 1.82, P=0.001), DBP (OR, 0.88, P=0.041), and fasting glucose (OR, 0.34, P<0.001) were independent predictors of stroke. Conclusions: Serum HO-1 level is higher in patients with stroke than TIA, but the bilirubin level is lower in patients with stroke than TIA and is an independent predictor of stroke. Further studies are warranted to clarify the underlying link among HO-1, bilirubin and stroke.