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Myofascial pain syndrome (MPS) is characterized by the presence of clinically detected myofascial trigger points (MTrPs). Diagnostic ultrasound (US) has been proposed as a method to strengthen the reliability of MTrP localization, thus potentially improving the efficacy and safety profile of interventional procedures. The objective is to evaluate the benefit and safety profile of any US-guided interventional procedure for MPS. Medline, Embase, PubMed, the Allied and Complementary Medicine Database (AMED), and Web of Science were systematically searched from their inception to May 2020 for any randomized controlled trial that evaluated treatment benefit and safety of any US-guided interventional procedure for MPS. The primary outcome of interest was pain severity. Additional outcomes of interest were function and adverse effects. The risk of bias was assessed using the Risk of Bias V.2.0 tool. eleven studies met all inclusion and exclusion criteria. Two studies (n=174) with a high risk of bias revealed some evidence supporting US guidance over blinded interventions for improvement in pain and function. Eight studies (n=483) with varying risks of bias were of head-to-head comparisons of different US modalities. These studies revealed that US-guided local anesthetic injections were inferior to US-guided pulse radiofrequency and US-guided dry needling (DN). US-guided DN was also found to be superior to US-guided platelet-rich-plasma injections but inferior to US-guided miniscalpel. Meanwhile, one study (n=21) with some concerns of bias found that US-guided local anesthetic injections were superior to non-steroidal anti-inflammatory drugs for pain outcomes and fewer adverse events. All US-guided procedures resulted in zero or minimal self-limited adverse events. Issues with clinical relevance, limited sample sizes, and small point estimates warrant more high-quality research to better characterize the possible value of US-guided injections., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)