Stroke in the young is attributed to the prevalence of thrombophilia, however, reports explaining the cause mechanisms from Indian populations are largely not known. The information about the association of inherited thrombophilia and occurrence of stroke is still missing. Therefore, we describe here 52 cases of young ischemic stroke of which 22 cases were of recurrent stroke and 30 cases of first episode stroke along with an equal number of healthy controls. Imaging techniques (CT/MRI/Doppler studies) were used to identify the type and location of infarcts among various regions of the brain. All the patients and controls were screened for hypercoagulable state by employing Pro C global test. Those tested positive for the latter were evaluated for conventional thrombophilic factors, activity levels of protein C and protein S, antithrombin III levels, plasma homocysteine levels and presence of activated protein C resistance, lupus anticoagulant, methylenetetrahydrofolate reductase (MTHFR C677T) and prothrombin G20210A polymorphisms. Out of 52 cases there were 22 cases of recurrent stroke and 30 cases of first ischemic stroke. Infarcts were single in 39 out of 52 cases and multiple in 13 cases. Among the different regions of brain internal capsule infarcts were seen in 13 of 52 (25%) cases, and cerebellum, basal ganglion and midbrain infarcts were seen in five cases (9.6%) each and remaining infarcts were in other anatomical regions of the brain. Left middle cerebral artery territory was involved in 17 of 52 (32.7%) cases. The prevalence of individual thrombophilia among cases ranged from 28.8% (15/52) for protein S and 11.5% (6/52) for protein C deficiencies respectively. All cases of protein C were protein S deficient. Five cases of protein C deficiency patients were of 25 years and younger as compared with one case in the at least 25 years age group. Plasma homocysteine levels were elevated in three cases (5.7%) as compared with normal levels in controls. Homozygous MTHFR C677T was seen in three cases, whereas heterozygosity for the same was observed in five cases. Out of three homozygous cases for C677T MTHFR polymorphism, two of these patients had hyperhomocysteinemia. None of the five cases of heterozygous C677T MTHFR polymorphism had hyperhomocysteinemia. All patients were found to be negative for prothrombin G20210A mutation. The results of the present study suggest that protein S deficiency alone or protein S deficiency in combination with protein C deficiency as well as hyperhomocysteinemia are significantly associated with ischemic stroke in young Indians.