Background: Osteoarthritis (OA) is one of the major cause of morbidity, having a substantial influence on health quality of life, imposing enormous burden of cost on the health care system. It is a chronic degenerative disorder that is characterised by articular cartilage degeneration. It can be caused by aging, heredity and injury from trauma or disease. Primary symptoms of OA include joint pain, stiffness and limitation of movement. Disease progression is usually slow but can ultimately lead to joint failure with pain and disability. Stromal vascular fraction (SVF) derived from adipose tissue is a rich source of pre adipocytes, mesenchymal cells (MSC), endothelial progenitor cell, T cells, B cells, mast cells as well as adipose tissue macrophages. It can be easily obtained from loose connective tissue that is associated with adipose tissue by lipoaspiration under local anaesthesia. SVF is isolated without using any enzymes or chemicals and its autologous grafting is done in a single surgical sitting. Here, we evaluated safety and clinical efficacy of freshly isolated Autologous SVF cells in patients with grade 2-4 degenerative osteoarthritis (OA). . Methods: A total of 116 joints mainly knee OA were treated with autologous grafting of SVF done in a single surgical sitting. A total of 116 joints studied out of which 80 joints were followed up for 12 months, 88 joints followed for 9 months, 110 joints followed for 6 months and finally all 116 joints were followed for minimum 1 month for safety and efficacy. Results: Modified KOOS clinical score was used to evaluate clinical effect and was based on pain, non-steroid analgesic usage, limping, extent of joint movement, and stiffness evaluation before and at pre-operative, 1 Month post-op, 6 months post-op and 12 Months post-op after grafting. No side effects, systemic infection or cancer was associated with Autologous grafting of SVF. There was a significant improvement from pre-op to post op in all the followed patients. Average KOOS score improved from pre-operative 46.4 to post-operative 12 months average 77.9 i.e. very significant improvement in all grades. All sub-scale parameter for pain, symptoms, activity of living and quality of life showed significant improvement. Higher grade of OA were associated with comparatively slower healing. Conclusions: Autologous grafting of SVF in single surgical sitting is a novel and promising treatment approach for patients with degenerative OA. This treatment method was found to be minimal invasive, safe and cost-effective treatment modality for osteoarthritis.