Background: Symptomatic intracranial atherosclerotic disease (sICAD) is associated with risk of recurrence of cerebral ischemic events in 4-19% of stroke patients annually. Previous studies indicate elevated high-sensitivity C-Reactive Protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) to be associated with risk of recurrence. Objective: This prospective, observational study investigated serum levels of hs-CRP and the activity of Lp-PLA2 in patients with sICAD in predicting the risk of long-term stroke recurrence. Methods: We enrolled 48 patients with sICAD at 3 months from onset. The demographics, clinical, and imaging characteristics were recorded. Serum hs-CRP and Lp-PLA2 activity were assessed using automated high-sensitivity C-reactive protein assay and photometric technique, respectively. Patients were followed up at 6 months and 1 year and the presence of new vascular events was recorded. Results: The mean age of our study population was 59.5 ± 10.3 years and 91.7% were men. Four patients developed recurrent strokes during follow-up. The mean Hs-CRP was elevated in patients with events than in patients without events (5.9 ± 10.4 mg/L vs. 1.7 ± 2.4 mg/L, P=0.03). However, there was no significant association of mean Lp-PLA2 activity (118.3±42.9 nmol/min/ml vs. 111.9 ± 34.2 nmol/min/ml, P=0.73) with recurrence. Elevation of hs-CRP (3.02 ± 4.8 mg/L vs. 0.95 ± 0.57mg/L, P=0.02) and Lp-PLA2 activity (120.1±40.3 nmol/min/ml vs. 103.3 ± 23.9 nmol/min/ml, P=0.04) was correlated with high-grade stenosis in these patients. Conclusion: Our study suggests serum levels of hs-CRP may serve as a predictor of long-term stroke recurrence risk in sICAD and elevation of hs-CRP and Lp-PLA2 correlated with the severity of stenosis in symptomatic intracranial atherosclerotic disease.