The role of nimodipine and milrinone in the management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) was studied using clinical and TCD (transcranial Doppler) parameters. In this prospective observational study, patients with DCI after aneurysmal SAH presenting between November 2020 and June 2021 who were treated by either intra-arterial nimodipine (IAN) or intravenous milrinone (IVM) were included after excluding patients in whom both IAN and IVM had been given or mechanical angioplasty was performed. Twelve-hourly TCD was performed during the course of the therapy. Clinical improvement and the development of new brain infarcts were also assessed. A P value <0.05 was considered statistically significant. Thirty-four patients fulfilled the inclusion criteria (IVM, 13/34 [38%]; IAN, 21/34 [62%]); patients in the IVM group (vs. IAN group) had poorer median Glasgow Coma Scale score (12 vs. 13), poorer motor response (<M6 response, 5/13 [38%] vs. 5/21 [24%]; P= 0.36) and higher grades (modified Fisher grade ≥3) of SAH (12/13 [92%] vs. 8/21 [86%]; P= 0.56). More patients in the IAN group (vs. IVM group) showed clinical improvement (17/21 [81%] vs. 10/13 [77%]; P= 0.77), development of new infarcts (15/21 [71%] vs. 7/13 [54%]; P= 0.29] and discharged to home (13/21 [62%] vs. 6/13 [46%]; P= 0.36) with less mortality (1/21 [9%] vs. 4/13 [23%]; P= 0.037). On TCD analysis, both IAN and IVM protocols showed similar effects in middle cerebral artery vasospasm; however, IAN proved better over time. In group-effect analysis, the IAN protocol was significantly better in anterior cerebral artery and posterior cerebral artery vasospasm compared with IVM protocol. In this single-center small study, patients in the IAN group had significantly less mortality compared with the IVM group in the management of DCI after aneurysmal SAH.