This systematic review with meta-analysis sought to determine the efficacy and safety of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) on clinical outcomes following percutaneous coronary intervention. Medline, Embase, Elsevier, and web of knowledge as well as Google scholar literature were used for selecting appropriate studies with randomized controlled design. After screening 445 studies, a total of 23 trials (including a total of 43,912 patients) were identified that reported outcomes. Pooled analysis revealed that LMWH compared to UFH could significantly increase thrombolysis in myocardial infarction grade 3 flow (p < 0.001), which was associated with similar target vessel revascularization (p = 0.6), similar incidence of stroke (p = 0.7), and significantly lower incidence of re-myocardial infarction (p < 0.001), major bleeding (p = 0.02) and mortality (p < 0.001). Overall, LMWH was shown to be a useful type of heparin for patients with MI undergoing PCI, due to its higher efficacy and lower rate of complication compared to UFH. It is also associated with increased myocardial perfusion, decreased major hemorrhage, and mortality.