Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. EG-1962 is a sustained release formulation of nimodipine for intraventricular delivery into the subarachnoid space while avoiding dose-limiting hypotension common with systemic administration. We conducted a phase 1/2a multicenter, controlled, randomized, open label, dose escalation study to determine the maximum tolerated dose (MTD) and assess safety, tolerability, pharmacokinetics and clinical outcome at 90 days on the extended Glasgow outcome scale (GOSE) of a single intraventricular dose of EG-1962 (http://www.clinicaltrials.gov Identifier: NCT01893190). Subjects with aSAH repaired by clipping or coiling were randomized within 60 hours of aSAH to EG-1962 or oral nimodipine if they were World Federation of Neurological Surgeons grade 2 to 4 and had a ventricular catheter. Cohorts of 12 subjects received 100, 200, 400, 600, 800 or 1200 mg EG-1962 (9 per cohort) or oral nimodipine (3 per cohort). The MTD was 800 mg EG-1962. Plasma nimodipine concentrations after administration of EG-1962 were sustained for 21 days and increased in a dose-dependent fashion. Cerebrospinal fluid nimodipine concentrations with EG-1962 were orders of magnitude higher than in plasma and with oral nimodipine. There was one serious adverse event (possible allergic reaction) related to EG-1962 (400 mg) and two EG-1962 dose limiting toxicities (increased intracranial pressure, 400 and 800 mg); all were without clinical sequelae. There was no EG-1962-related hypotension as compared to hypotension in 17% (3/18) with oral nimodipine. Favorable outcome (GOSE 6-8) was achieved in 27 of 45 (60%) EG-1962 subjects (5 of 9 with 100, 6 of 9 with 200, 7 of 9 with 400, 4 of 9 with 600 and 5 of 9 with 800 mg) and 5 of 18 (28%) oral nimodipine subjects. Improved efficacy was supported by reduction in delayed cerebral ischemia (15/45 [33%] EG-1962 versus 11/18 [61%] oral nimodipine) and rescue therapy (11/45 [24%] versus 10/18 [56%]) in EG-1962 subjects. Intraventricular EG-1962 was safe and tolerable to 800 mg, associated with sustained and dose-dependent nimodipine plasma concentrations,improved clinical outcome and reduced delayed cerebral ischemia and use of rescue therapy after aSAH.