OBJECTIVE: The objective of this review was to synthesize the best available research evidence regarding the effectiveness of physical stimulation for reducing injection pain in adults receiving intramuscular injections. INTRODUCTION: Pain associated with intramuscular injections continues to be a challenge for nurses. Various physical stimulation methods to alleviate pain and improve satisfaction for patients receiving intramuscular injections have been reported; however, the evidence surrounding the effectiveness of these methods remains inconclusive. INCLUSION CRITERIA: This systematic review considered randomized and quasi-experimental studies that used any physical stimulation strategies (eg, skin tapping, manual pressure, massage, pinch, traction) for adults aged 18 years and over receiving intramuscular injections. Studies that evaluated pain using validated instruments were considered for inclusion. METHODS: A three-step search strategy was conducted. MEDLINE, Embase, CINAHL, the Cochrane Library (Cochrane CENTRAL), Google Scholar, Dissertation Abstracts International, ProQuest Dissertations and Theses, and MedNar were searched from inception until 2020. We restricted the inclusion of studies to trials published in English. Two independent reviewers conducted the critical appraisal of eligible studies using the JBI checklists for randomized controlled and quasi-experimental trials. Data were extracted using the JBI data extraction tool, and meta-analysis and subgroup analysis were undertaken, where appropriate. RESULTS: Twenty-five studies were included with a total sample size of 1956 patients. Pooled results demonstrated that pain was significantly less with the use of the Helfer skin tap technique compared to no intervention (two studies; RR 0.73; 95% CI 0.66, 0.81; P <0.00001) or standard intervention (three studies; SMD -2.25; 95% CI -3.65, -0.85; P =0.002). Intervention with acupressure using standard treatment as control showed significant reduction in pain intensity (MD -4.78; 95% CI -5.32, -4.24; P <0.00001). Similarly, pain was significantly lower with manual pressure (two studies; SMD -0.42; 95% CI -0.69, 0.15; P =0.002) when compared to standard treatment. Pain scores were significantly lower in patients who received pinch technique, ShotBlocker, massage, or combination intervention (skin traction, pressure, and rapid muscle release) compared with no intervention, standard treatment, or placebo control. CONCLUSIONS: The evidence from this review demonstrates that physical stimulation - particularly the Helfer skin tap technique, acupressure, manual pressure, pinch technique, ShotBlocker, massage, and combination - can significantly lower intramuscular injection pain; however, this is based on low or very low certainty of evidence. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020168586.