Hypercoagulable states represent a condition with multiple etiologies in which an interplay of acquired and congenital coagulation defects contribute to abnormal clotting. Several of the thrombophilic disorders are relatively prevalent; one person may have multiple defects, leading to thrombosis without obvious external stimuli. Factor V Leiden thrombophilia is the most common inherited form of thrombophilia and it is occasionally associated with the anomalous prothrombin G20210A mutations. We presents three puertorrican middle-aged females diagnosed with Factor V Leiden after debuting with abnormal clotting events. They shared the common traits of being female, having been born in Puerto Rico, and having parents of European descent. The first two cases presented with deep venous thrombosis of lower and upper extremities, and both had the association of Factor V Leiden and prothrombin G20210A mutation. The third case presented with a cerebrovascular accident, evidencing arterial thrombosis, after receiving estrogen replacement therapy. This report adds Factor V Leiden as a cause of hypercoagulable states in puertorrican patients.