Unfractionated heparin (UFH) is frequently administered before percutaneous coronary intervention in patients with ST segment elevation myocardial infarction (STEMI). Current guidelines, however, do not provide clear recommendations for UFH pretreatment before arrival at the coronary catheterization laboratory. Between June and July 2023, we systematically searched PubMed, Embase, and Cochrane databases for studies comparing UFH pretreatments in patients with STEMI. A random-effects meta-analysis and meta-regression analyses were performed. Fourteen studies were included, of which four were randomized clinical trials. A total of 76 446 patients were included: 31 238 in the pretreatment group and 39 208 in the control group. Our meta-analysis revealed lower all-cause mortality for the pretreatment strategy when compared with the control group, albeit with high heterogeneity [pooled odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.49-0.76, P < 0.01; I2 = 77%]; lower in-hospital cardiogenic shock (pooled OR = 0.68, 95% CI: 0.58-0.78, P < 0.21; I2 = 27%) and a higher rate of spontaneous reperfusion events (pooled OR = 1.68, 95% CI: 1.47-1.91, P < 0.01; I2 = 79%). In terms of major bleeding, the UFH pretreatment strategy further revealed a decreased rate of events (pooled OR = 0.85, 95% CI: 0.73-0.99, P = 0.40; I2 = 4%). Our study suggests that UFH pretreatment in patients with STEMI undergoing primary percutaneous coronary intervention was associated with reduced all-cause mortality, cardiogenic shock, enhancing reperfusion rates while diminishing major bleeding events.