Objective Stem cell injection for knee osteoarthritis (KOA) is an emerging new therapy, and we aimed to review its evidence of efficacy.

Design Systematic review.

Eligibility criteria Criteria for eligibility were randomised controlled trials (RCTs) and non-RCT on the efficacy of stem cell injections in KOA. All references were checked for missed articles.

Data sources MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library, PEDro and SPORTDiscus were searched. A grey literature search was performed. No restrictions were imposed to our search strategy.

Risk of bias and data synthesis Risk of bias was assessed using the Cochrane risk of bias tool. Descriptive synthesis was performed using the levels of evidence according to the Oxford Levels of Evidence.

Results Five RCTs and one non-RCT were found. Bone-marrow-derived stem cells, adipose-derived mesenchymal stem cells and peripheral blood stem cells were used. All trials were at high risk of bias, resulting in level-3 evidence. All five RCTs reported superior efficacy for patient-reported outcomes (Visual Analogue Scale, Western Ontario and McMaster Universities Arthritis Index, Tegner, Lysolm, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Lequesne) compared with controls at final follow-up (range 24–48 months). Superior radiological outcomes were found favouring stem cell injection. Superior histological outcomes and/or improved arthroscopically scored healing rates were reported in two trials. No serious adverse events were reported.

Conclusion Six trials with high risk of bias showed level-3 or level-4 evidence in favour of stem cell injections in KOA. In the absence of high-level evidence, we do not recommend stem cell therapy for KOA.