Background: Adipose-derived mesenchymal stem cells (ADMSCs) have recently been studied for the treatment of knee osteoarthritis. The goal is pain reduction and improvement of joint function leading to superior health-related quality of life. Objectives: The aim of this study was to provide a comprehensive meta-analysis assessing the evidence on the use of ADMSCs in knee osteoarthritis. Design: This is a Meta-analysis of randomised controlled trials. Data Sources and Methods: PubMed/MEDLINE, Embase, and Cochrane Databases were searched for randomized controlled trials using ADMSCs to treat patients with knee osteoarthritis. Only trials comparing ADMSCs to placebo or conservative treatment were included. The outcomes studied were improvement in functional, pain, and quality of life scores along with radiographic findings. Results: A total of four trials were included, representing 138 patients with knee osteoarthritis. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores favored ADMSCs with a statistically and clinically significant difference over controls at 6- and 12-month follow-ups (p value < 0.0001). Pain, functional, and quality of life scores also favored ADMSCs at 12-month follow-up (p value < 0.0001). Conclusion: ADMSCs are effective in treating knee osteoarthritis symptoms as observed by functional and pain improvements. Furthermore, ADMSCs injection showed improvement of cartilage integrity, which indicates the potential for regenerating the knee cartilage. Future trials with larger number of patients and longer follow-up periods would help to elaborate further the therapeutic potential of ADMSCs. Plain Language Summary: Adipose-derived mesenchymal stem cells use in knee osteoarthritis Knee osteoarthritis is an extremely common disease that causes damage of the lining of the knee joint. This will lead to pain and limited range of motion of the knee hence limited functionality. Multiple treatments are used currently for knee osteoarthritis which all aim at slowing down the progression and limiting the need for knee replacement surgery. Adipose-derived mesenchymal stem cells (ADMSCs) are stem cells harvested from the fat around the belly. These stem cells have the potential to be converted into cells of a certain origin (cartilage, muscle, fat). Many studies are being performed to see whether these cells can transform to cartilage and repair the damaged knee joint. In this study, we tried to find how the results of different studies comparing the usual treatments for knee osteoarthritis with that of ADMSCs compared. We were mostly interested in the pain, functional, stiffness, and quality of life scores. We also reviewed the MRI findings to find out whether the lining of the knee joint improved. Four studies were included with 138 patients having knee osteoarthritis. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score which is a self-administered questionnaire evaluating hip and knee osteoarthritis, showed better results in patients receiving ADMSC injections compared with other usual treatments at 12-month follow-up. Pain, functional, stiffness, and quality of life scores also showed better results in ADMSCs at 12-month follow-up. MRI images also showed better cartilage lining in the patients treated with ADMSCs. We concluded that ADMSCs are both effective and safe to be used in treating knee osteoarthritis symptoms. However, studies with longer follow-up periods are needed to better assess the regenerative potential of ADMSCs. [ABSTRACT FROM AUTHOR]