There are few reports on valproic acid related to thrombophilia. Thrombophilic risk factors were investigated in 21 children (age range, 1-13 years) diagnosed with epilepsy and newly treated with valproic acid monotherapy. None of the children had been previously treated with any anticonvulsant agent. Before starting valproic acid therapy, homocysteine, lipoprotein(a), factor VIII, factor IX, protein C, protein S, antithrombin III levels, and activated protein C resistance levels were evaluated in all patients, with repeat evaluation after 9 months or 1 year of the therapy. Thrombosis gene mutations (factor V Leiden and prothrombin G20210A) were also evaluated in all patients before therapy. There was statistically significant elevation in lipoprotein(a) levels and reduction in fibrinogen levels after treatment. Reduction in protein C levels and elevation in homocysteine levels were also observed, but without statistical significance. Before therapy, no thrombotic event had occurred, despite thrombotic risk factors in some patients. Valproic acid can increase lipoprotein(a) and decrease fibrinogen, which may increase the risk of stroke or other thrombotic events. No clinical adverse effects resulted from changes in the levels or activity of thrombophilic factors associated with valproic acid treatment. Thus, routine investigation of factors implicated in thrombosis prior to initiation of valproic acid is not warranted for all patients. Nonetheless, caution is advised when initiating valproic acid treatment in children who have had prior stroke or thrombotic events.