Purpose <p>We sought to investigate the efficacy and safety of local nitroglycerin (NTG) application in facilitating radial artery cannulation in adults.</p> Methods <p>In February 2024, we searched PubMed®, Embase, EMCARE, and the Cochrane Library. Local NTG could have been subcutaneous injection or topical application. We sought to conduct a meta-analysis using Hartung–Knapp adjustment of the DerSimonian–Laird random effects model.</p> Results <p>We included 15 randomized controlled trials (RCTs) (<i>n</i> = 2,370), of which 4 (<i>n</i> = 423) evaluated topical NTG, whereas 11 (<i>n</i> = 1,947) used subcutaneous infiltration. All 4 trials evaluating topical NTG and 9/11 evaluating subcutaneous NTG used ultrasound to facilitate radial artery cannulation, whereas this was unclear in 2/11 trials evaluating subcutaneous NTG. The majority of studies had an unclear risk of bias (ROB). All 15 studies reported NTG to be beneficial. The meta-analysis found that subcutaneous NTG was associated with increased rates of first-attempt success (risk ratio [RR], 1.61; 95% confidence interval [CI], 1.23 to 2.10; five studies; 516 patients) and decreased risk of radial artery spasm (RR, 0.43; 95% CI, 0.24 to 0.77; seven studies; 1,519 patients). Topical NTG was associated with increased rates of first-attempt success (RR, 2.45; 95% CI, 1.39 to 4.34; one study; 92 patients) but resulted in little or no difference to the incidence of radial artery spasm (RR, 0.67; 95% CI, 0.20 to 2.25; three RCTs; 275 patients). The overall certainty of evidence was low.</p> Conclusions <p>Topical or subcutaneous NTG has the potential to facilitate radial artery access and decrease local complications. Given that the certainty of evidence was low, additional RCTs are needed.</p> Study registration <p>PROSPERO (<a href="https://www.crd.york.ac.uk/PROSPERO/view/342158">CRD42022342158</a>); first submitted 29 June 2022.</p>