Aims To assess the effectiveness of physical-procedural interventions in reducing pain during intramuscular injections. Design Systematic review and meta-analysis. Method English keywords were used to search databases [MEDLINE (OVID, Ebsco), SCOPUS, Science Direct, COCHRANE and the reference lists from retrieved articles] from their inception to November 2017 and randomized and quasi-experimental trials were selected based on inclusion and exclusion criteria. The standardized mean difference and random effects model were used. Results From 2,318 articles, 15 articles (1996-2017) met the criteria for the meta-analysis. Physical-procedural interventions described in the articles were included in this systematic review. The overall standardized mean difference was 0.595 (95% confidence interval (CI) = 0.417-0.773), indicating a moderate effect on pain levels. Generally, these interventions (two-needle technique, acupressure, manual pressure, ShotBlocker, Z-technique, air-lock technique, injection site postinjection massage, and speed of injection) have been found to moderately reduce pain. Conclusion It seems difficult to conclude that a single intervention reduces pain in adults. However, we can state that the most effective interventions for reducing pain during intramuscular injections in adults involve the ventrogluteal site, the Z-technique, and manual pressure. Impact The systematic review will provide guidance to clinicians, staff, and educator nurses and future studies. The systematic review will help nurses and educators apply techniques based on evidence in any setting. The systematic review will guide well-designed and well-reported studies to contribute to the accumulation of evidence in nursing research.