The anatomic variation of Circle of Willis (CoW) has great impact on its compensatory capacity during stroke and cerebral ischemia. In the present study, a series of lumped parameter models were developed and used to simulate the effect of postural changes on the cerebral blood flow in ICA stenosis patients with different anatomic variants of the CoW. The results showed that the asymmetric distribution of cerebral blood flow caused by stenosis was attenuated in standing position in complete and half-complete CoW. However, in incomplete CoW, the decrease in blood flow in the ipsilateral cerebral arteries caused by unilateral ICA stenosis was dramatic in both supine and standing positions, a likely result of inadequate collateral circulation within the CoW. In conclusion, the anatomic variation of CoW plays a significant role in maintaining the balance of cerebral blood supply in patients with ICA stenosis, especially during postural change.