Objective This study aims to investigate the influence of cerebral hemodynamic changes during headache-free periods on the efficacy of migraine prophylaxis. Methods Fifty-two children with migraine were given a TCD test during headache-free periods and then Normal TCD and Abnormal TCD groups were selected according to the TCD findings. Each group was randomly given either flunarizine or cyproheptadine treatment. The efficacy was evaluated with Bussone scores after 4 months of treatment. Results Bussone scores of patients treated with flunarizine were significantly lower than those of patients treated with cyproheptadine in the Abnormal TCD group ( 5.69± 4.15 vs 15.92± 10.52; P< 0.05). In the Normal TCD group, the patients treated with cyproheptadine had lower Bussone scores than those treated with flunarizine ( 6.43± 6.62 vs 17.46± 11.62; P< 0.01). Conclusions The efficacy of migraine prophylaxis may be improved by selecting rational drugs based on cerebral hemodynamics changes during headache-free periods.