INTRODUCTION: Regenerative therapy has shown promising results in the treatment of osteoarthritis (OA) knee with Kellgren-Lawrence (KL) Grades I-III. We compared the safety, efficacy, functional, and clinical outcomes of intra-articular implantation of autologous adipose tissue-derived stromal vascular fraction (SVF) isolated using direct ultrasonic cavitation (Sahaj therapy-Cell Innovation Patented Technology) and saline injection in knee osteoarthritis. MATERIALS AND METHODS: The present prospective observational study was conducted over 3 years. We enrolled 120 patients in our study, where four patients got excluded as they did not meet the inclusion criteria. The remaining 116 patients were randomized into two groups, one with autologous adipose tissue-derived SVF and the other group with saline injection. A comparison of mean KOOS and VAS scores at different follow-ups was done using Paired '' test. A value of < 0.05 was considered significant. RESULTS: The results show that the SVF group had significantly higher KOOS scores (78.49 ± 6.54 in the SVF group vs 59.19 ± 5.14 in the saline group), respectively (0.001). Similarly, the SVF group had significantly lesser VAS scores (3.17 ± 0.94 in the SVF group vs 3.89 ± 1.04 in the saline group), respectively (0.001). CONCLUSIONS: Autologous adipose tissue-derived SVF is a better choice for treating knee osteoarthritis. For individuals with degenerative osteoarthritis, autologous SVF grafting in the same surgical procedure is an innovative and promising treatment modality. Even after 3 years of follow-up, the study participants with OA knee have shown a good clinical and functional outcome.