Recent randomized clinical trials of a single infusion of mesenchymal stem cells (MSCs) for acute cerebral stroke revealed a limited functional recovery outcome. Conversely, animal studies suggest that multiple MSC infusions may enhance functional recovery by inducing neural plasticity, which indicates that a multiple-infusion approach might be effective for stroke treatment in humans. The objective of this study was to investigate whether multiple infusions of MSCs enhance functional outcomes during the acute phase of cerebral ischemia.