OBJECTIVE: Myofascial pain is a chronic pain disorder characterized by the presence of painful localized regions of stiff muscle and/or myofascial trigger points. Intramuscular myofascial trigger point injections are considered first-line treatments for myofascial pain. Common injectates include local anesthetics and botulinum toxin-A (BTX-A). The objective of this systematic review was to compare the effectiveness of local anesthetics and BTX-A on pain intensity in patients with myofascial pain. METHODS: A comprehensive systematic search of 3 databases, EMBASE, CENTRAL, and Medline was conducted. The search was comprised of words to describe "myofascial pain" and "injections." We performed a meta-analysis comparing local anesthetic and BTX-A injections across these follow-up week periods: 0 (immediately following the injection), 1 to 2, 3 to 4, 5 to 6, 7 to 8, 9 to 10, 11 to 12, 16, 18, 24 weeks with local anesthetics and BTX-A as subgroups. We also performed subgroup analyses comparing the effectiveness of local anesthetic injections and BTX-A injections at various muscle locations and comparing the effectives of single versus multiple injection sessions. RESULTS: In total, 33 studies were included. A qualitative analysis suggested that local anesthetics and BTX-A were inconsistently effective at mitigating pain across all follow-up periods. The meta-analyses revealed that local anesthetic injections were more effective than BTX-A at mitigating pain intensity. Multiple injection sessions of local anesthetics were more beneficial than a single session. CONCLUSIONS: Additional studies are needed to determine sources of heterogeneity mediating the observed differences in effectiveness of local anesthetic and BTX-A injections among the studies. Additional replicative studies are also needed to delineate the relative efficacy and effectiveness of local anesthetic and BTX-A injection. The quantitative results of this study suggest that patients overall experience more pain relief with local anesthetic injections.