Abstract Objective Assess the efficacy of single and multiple intra-articular injections of autologous adipose-derived stem cells (ASCs) and adipose-derived stromal vascular fraction (ADSVF) for the treatment of knee osteoarthritis (OA). Methods We conducted a thorough and systematic search of several databases, including PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, to identify relevant studies. The included studies were randomized controlled trials (RCTs) that involved single or multiple intra-articular injections of autologous ASCs or ADSVF for the treatment of patients with knee osteoarthritis, without any additional treatment, and compared to either placebo or hyaluronic acid. Results A total of seven RCTs were analyzed in this study. The results of the meta-analysis show that compared to the control group, both single and multiple intra-articular injections of ASCs or ADSVF demonstrated superior pain relief in the short term (Z = 3.10; P