© 2017 Elsevier B.V. Objective To compare the outcome of patients with acute ischemic stroke who received or did not receive intravenous fluid. Patients and methods This study was a prospective, multicenter, randomized, open-label trial with blinded outcome assessment. We enrolled acute ischemic stroke patients without dehydration aged between 18 and 85 years with NIH Stroke Scale score (NIHSS) score from 1 to 18 who presented within 72 h after onset. Patients were randomly assigned to receive 0.9% NaCl solution 100 ml/h for 3 days or no intravenous fluid. Results On the interim unblinded analysis of the safety data, significant excess early neurological deterioration was observed among patients in the non-intravenous fluid group. Therefore, the study was prematurely discontinued after enrollment of 120 patients, mean age 60 years, 56.6% male. Early neurological deterioration (increased NIHSS ≥3 over 72 h) not of metabolic or hemorrhagic origin was observed in 15% of the non-IV fluid group and 3.3% of the IV fluid group (p = 0.02). Predictors of neurological deterioration were higher NIHSS score, higher plasma glucose, and increased pulse rate. There was no difference in the primary efficacy outcome, NIHSS ≤ 4 at day 7, 83.3% vs 86.7%, p = 0.61 or secondary efficacy outcomes. Conclusion Administration of 0.9% NaCl 100 ml/h for 72 h in patients with acute ischemic stroke is safe and may be associated with a reduced risk of neurological deterioration. These study findings support the use of intravenous fluid in acute ischemic stroke patients with NIHSS less than 18 who have no contraindications.