OBJECTIVES: The objective of this study was to review the trends in design of pivotal clinical trials of stem cells for treatment of stroke. METHODS: Systematic review was conducted to identify new and on-going pivotal clinical for stroke. The inclusion criteria were the indication of stroke, treatment with stem cells and study completion date of 2016 or after. The data field extracted were study title, intervention, sponsor, age subgroups, planned enrollment, study type, study design, completion date and outcome measures. RESULTS: Overall, 16 clinical studies with total planned enrollment of 755 patients were identified. The median enrollment for the studies was 34 patients. All of the studies were for stem cell transplantation (majority were autologous, only two were allogenic). The primary outcome measures varied significantly across trials. The change in Change from baseline in Fugl-Meyer Scale was the most common (4 out of 16 trials) outcome across these trials. Other primary outcome measures included: Functional Independence Measure, Action Research Arm Test, Improvement in power of Body and facial Muscles and Categorical shift in modified Rankin scale (mRS). The secondary outcome measures also varied significantly across trials. The secondary outcomes included: Change from baseline in NIH Stroke Scale at 12 months, Speech Therapy Specific Neuropsychological outcome measures, Comparison of modified Rankin scale (mRS), Distinguish of EuroQol 5d (EQ-5D) between pre- and post-treatment 180 days, restoring upper limb function following an ischemic stroke using the ARAT, Changes in Barthel index (BI) and Mini-Mental State Examination. CONCLUSIONS: Lack of consistent primary and secondary outcomes across stem cell treatments for stroke might pose some challenges in demonstrating value to various stakeholders.