In recent years, iron-deficiency anemia (IDA) has been suggested to have an association with childhood-onset ischemic stroke in otherwise healthy children, but few cases have proven it thus far. In this study, we aimed to investigate whether iron-deficiency anemia is a risk factor for cerebrovascular events and childhood-onset ischemic stroke in previously healthy children. This was a case-control study that included 21 stroke cases with patients who had previously been generally healthy, and matched with age and gender of 100 healthy control subjects. Patients were included if a diagnosis of definite stroke had been made and other known etiologies of childhood onset stroke were excluded. For all subjects, iron parameters including serum iron, ferritin, transferrin, total iron binding capacity, and transferrin saturation were assessed. We screened all case patients for prothrombotic factors including level of hemoglobin S, protein C, protein S, antithrombin III, lupus anticoagulant, factor V Leiden, and prothrombin gene mutation (G20210A). Brain magnetic resonance images (MRI), magnetic resonance angiography (MRA), and magnetic resonance venography (MRV) were performed to all case patients. All case patients have normal results regarding functional, immunological, and molecular assay for prothrombotic factors screening. Our results showed that IDA was disclosed in 57.1 % of stroke cases with no identified cause, as compared to 26 % of controls. Our study suggest that previously healthy children who developed stroke are 3.8 times more likely to have IDA than healthy children, who do not develop stroke (OR, 3.8; 95 % CI:1.3-11.2 P = 0.005). In addition, there was significant interaction between IDA and thrombocytosis among studied cases (OR, 10.5; 95 % CI, 1.0-152 P = 0.02). There were nonsignificant differences between stroke patients with IDA and those with normal iron parameters regarding stroke subtype (P > 0.05). Public health messages on the importance of early detection of iron-deficiency anemia in young children, especially in our developing countries so that it can be treated before a life-threatening complication like stroke develops.