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Background: Because human fetal ventral mesencephalic tissue grafts provide promising results in ameliorating Parkinson's disease–implicated motor dysfunctions, human fetal midbrain‐derived dopamine neuronal precursor cells are considered good candidates for cell‐based therapy for Parkinson's disease in that large quantities of cells can be supplied through a good manufacturing practice–compliant system. Objective: We conducted a prospective, phase I/IIa, dose‐escalation, open‐label "first‐in‐human" clinical trial with fetal neural precursor cells to assess their safety and therapeutic efficacy in patients with idiopathic Parkinson's disease. Methods: Fifteen patients were assigned to receive three different doses of cells (4 × 106, 12 × 106, and 40 × 106 cells) and completed a 12‐month follow‐up. The primary outcome was safety, by measuring the presence of grade 3 or higher cells according to National Cancer Institute guidelines and any contaminated cells. Secondary outcomes assessed motor and neurocognitive function, as well as the level of dopamine transporters, by positron emission tomography–computed tomography. Results: Although a pronation‐supination and hand/arm movement performance was remarkably enhanced in all three groups (all P < 0.05), the medium‐ and high‐dose‐treated groups exhibited significant improvement in Unified Parkinson's Disease Rating Scale Part III only up to 26.16% and 40%, respectively, at 12 months after transplantation without any serious clinical complications or graft‐induced dyskinesia in all patients. However, the motor improvements did not correlate with increase in the dopamine transporter on positron emission tomography images. Conclusions: Our results primarily demonstrate the safety and plausible dose‐dependent efficacy of human fetal midbrain‐derived dopamine neuronal precursor cells for idiopathic Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]