Objective: The purpose of the present study was to investigate the incidence of middle cerebral artery (MCA) stenosis by contrast-enhanced MR angiography (CE-MRA), and to evaluate the risk factors for significant (>50%) MCA stenosis in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods: 116 patients with NPC after radiotherapy were recruited into the irradiation group to investigate the incidence and degree of MCA stenosis by CE-MRA. The results were compared with those of the control group, which comprised 57 newly diagnosed patients with NPC who did not receive radiotherapy. Furthermore, the risk factors for significant MCA stenosis were evaluated. Results: There was a higher incidence of MCA stenosis in the irradiation group than in the control group in terms of patient number (p=0.000) and vessel involvement (p=0.000), respectively. The incidence of significant MCA stenosis in the irradiation group was 8.6% (10/116 patients) and 5.2% (12/232 patients) in terms of patient number and vessel involvement, respectively. However, no significant MCA stenosis was found in the control group. Univariate analysis showed that hypercholesterolaemia, T3-4 stage and longer time interval from radiotherapy were the risk factors related to significant MCA stenosis. Multivariate analysis demonstrated that only T stage was the independent risk factor for significant MCA stenosis development. Conclusion: The results showed that radiation can cause MCA stenosis in patients with NPC after radiotherapy, especially in those with T3-4 stage, and further study is needed. Advances in knowledge: Radiation-induced MCA stenosis exists in patients with NPC after radiotherapy, and its prevalence is more common in patients with clinical T3-4 stage.