Objective: To assess the benefit of intra-articular injection of Botulinum toxin A (BoNT-A) for chronic refractory joint pain regardless of joint or pathology. Data sources: The search was performed on Ovid MEDLINE(R) In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R), Ovid EMBASE, Web of Science, and Scopus inception through Week 12, 2016. Trial selection: Clinical randomized controlled trials that evaluated BoNT-A intra-articular injection in patients with refractory joint pain were included. Data extraction: Two independent reviewers conducted data extraction. Results: A total of 6 out of 284 records were included. The analysis indicated that a statistically significant decreased pain score was found in BoNT-A therapy group than control group with WMD=1.10 (95% CI: 0.35 to 1.85; P<0.001; I-2=95%); WMD=0.7 (95% CI: 0.09 to 1.32; P=0.02; I-2=0%) at week 4, and 8 after injection, respectively. WOMAC score was also significant decreased in BoNT-A therapy group than control group with WMD=4.71 (95% CI: 2.76 to 6.67; P<0.001; I-2=0%); WMD=3.67 (95% CI: 1.08 to 6.26; P=0.006; I-2=27%) at week 4 and12 after injection, respectively. There was no difference in adverse event between BoNT-A therapy group and control group with OR=1.25 (95% CI: 0.88 to 1.78; P=0.47; I-2=0%). Conclusion: As compared with conventional therapy, BoNT-A intra-articular injection have beneficial effects with improved pain score and WOMAC score in adult patients with refractory joint pain.