OBJECTIVES: To determine the epidemiological risk factors associated with stroke, examine their influence on stroke-related costs, and identify areas that need further research. METHODS: A systematic literature search was performed (1996-2006) using an exhaustive list of relevant search terms to identify articles published on epidemiology of stroke and associated risk factors, costs of stroke and economic impact of risk factors on stroke. Studies were identified through electronic Medline® and PubMed® searches. Manual review of bibliographies allowed determination of additional articles. RESULTS: Out of a total of 41 included studies, 26 studies focused on stroke-associated risk factors, while 15 studies examined the economic burden of stroke. Apart from age and race [African-Americans have the highest per-capita stroke costs ($25,782), followed by Hispanics ($17,201)], hypertension was the most prevalent clinical risk factor (58.1% to 75%), followed by diabetes. Relative risk for stroke was higher in women (increase of 2-6.5 fold) as compared to men (1.5-2 fold) with diabetes. Renal dysfunction, pregnancy, inflammation and infection, depression, chronic headache and migraine, metabolic syndrome, cancer, and AIDS were other risk factors identified. Total cost of stroke in United States was found to be approximately $58 billion [2006 American Heart Association]. Mean total cost per individual approximated $125,000. Subarachnoid hemorrhage was reported to be the costliest stroke sub-type. Hospitalizations and medications were the major cost components in stroke treatment. Studies have linked few risk factors, such as smoking and higher age, to increased stroke treatment costs, but the impact of the majority of risk factors on stroke costs has not been examined. CONCLUSION: Stroke has a significant economic impact on society, due to its morbidity and mortality burden. However, few studies have examined the impact of individual stroke-associated risk factors on stroke costs. Further research demonstrating economic link of common risk factors with stroke is warranted.