C-reactive protein (CRP) is associated with unfavorable outcome in patients with acute ischemic syndromes and in patients with chronic stable angina. Elevated CRP levels suggestive of heightened inflammatory state in vascular conditions are often associated with elevated interleukin-6 (IL-6) levels. The aim of our study was to show the predictive importance of CRP and IL-6 levels in patients with ischemic stroke that has not been fully elucidated. Design We studied 647 consecutive elderly patients ( > 65 years) with stroke who were documented with ischemic stroke, presence of significant carotid atherosclerosis and absence of atrial fibrillation. The study population included 150 patients (74 men, 76 women, mean age 74 ± 2) . Patients underwent evaluation of high sensitive CRP and II.-6 levels at baseline, during hospitalization and at discharge. Results In-hospital mortality was 6% , 1 year mortality was 15% and a second cerebrovascular event occurred in 12% of patients. Those with in-hospital events had significantly higher baseline CRP and IL-6 levels than patients without events (3.8 ± 1.1 vs 1.9 + 0.9 mg/L, P<0.01 and 13. 8 ±3.4 vs 6. 3 ±2.1 pg/ml, P<0.01, respectively). Also CRP and IL-6 levels were significantly higher in those patients with an event within 3 months of discharge compared to patients without an event (3.6 ± 1.3 vs 1.1 ± 0.7 mg/L, P <0.01 and 14.2 ± 3.7 vs 5.4 + 1.6 pg/ml, P<0.01, respectively). Both base line CRP levels and IL-6 were predictive of events both in-hospital and after 3 months while CRP and IL-6 levels at baseline were not associated with a poor 1 year prognosis. Elevated CRP levels were associated with an unfavorable outcome only when IL-6 levels were also elevated. In a stepwise multivariate analysis IL-6 level was a stronger predictor of outcome than CRP. Conclusions In conclusion, elevated CRP and IL-6 levels may identify elderly patients at increased medium term risk, but do not predict one year events in this subset of patients. CRP levels predict events only when they are coupled with IL-6 levels.