Previous studies have indicated a neuroprotective effect of remote limb ischemic preconditioning. The aim of the present study was to assess whether upper arm ischemic preconditioning is feasible and safe in patients with unilateral middle cerebral artery (MCA) stenosis compared to healthy volunteers. Ten patients with unilateral MCA stenosis and 24 healthy volunteers underwent limb ischemic preconditioning, consisting of five cycles of 5-min inflations of a blood pressure cuff to 200 mmHg around an upper limb followed by 5 min of reperfusion. Limb ischemic preconditioning has no significant effect on the heart rate, oxygenation index, or mean flow velocity in patients with unilateral MCA stenosis or healthy volunteers. However, healthy volunteers showed a reduction in blood pressure 30 min following reperfusion of the last cycle. Limb ischemic preconditioning was found to be safe and well tolerated in both patients and healthy volunteers. We highlight the potential of limb ischemic preconditioning as an adjunct to neuroprotective treatment.