Background: The alarming disability burden and a high prevalence rate of stroke in India has encouraged the researchers to develop regenerative therapies to reduce clinical deficits. This study evaluates safety, feasibility and efficacy of autologous mononuclear and mesenchymal cell transplantation in stroke patients evaluated on clinical scores and functional imaging (fMRI and DTI). Methods: Forty (n = 40) stroke patients were recruited with the inclusion criteria as: 3 months to 2 years of index event, power of hand muscles of at least 2; Brunnstrom stage: 2-5; conscious and comprehendible. Fugl Meyer (FM), modified Barthel Index (mBI), Medical Research Council (MRC) grade for strength, Ashworth tone scale and functional imaging was used for assessments at baseline, 8 weeks and 24 weeks. 50-60 million cells in 250 ml saline were infused intravenously over 2-3 h. Results: The safety test profile was normal with no mortality or cell related adverse reactions in stem cell patients. Among outcome parameters, only modified Barthel Index (mBI) showed statistical significant improvement (p < 0.05) in the stem cell group. An increased number of cluster activation in Brodmann areas BA 4, BA 6 was observed post stem cell infusion indicating neural plasticity. Conclusion: Autologous intravenous stem cell therapy is safe and feasible. Stem cells act as "scaffolds" for neural transplantation and may aid in repair mechanisms in stroke. © 2012 Elsevier B.V. All rights reserved.