Objectives –  The aim of this study was to compare the effects of antihypertensive agents on cerebral blood flow (CBF) in hypertensive patients with previous ischemic stroke. Materials and methods –  In this double‐blind, multi‐center, non‐inferiority trial, 196 patients were randomized to cilnidipine 10–20 mg or losartan 50–100 mg once daily for 4 weeks. Baseline and follow‐up CBF as measured by single photon emission computed tomography were obtained in 167. The primary endpoint was the global CBF change. The secondary endpoints were the CBF change in the hemisphere ipsilateral to the index stroke, non‐impairment of global CBF and blood pressure (BP) reduction. Results –  Global CBF increased significantly in the cilnidipine arm (9.0 ± 29.6%, P = 0.0071) and the losartan arm (11.4 ± 31.4%, P = 0.0012), and these changes were not different between the two groups (P = 0.607). However, the estimated difference in percentage global CBF change between the two groups was −2.43% (97.5% CI, −13.06% to 8.21%), which crossed the predetermined non‐inferiority margin of −8.6%. Ipsilesional hemispheric CBF change, non‐impairment of global CBF and BP reduction were similar in the two groups. Conclusions –  This trial failed to prove the non‐inferiority of cilnidipine to losartan regarding global CBF change. Both the treatments, however, increase the global CBF despite BP lowering.