Introduction: As per international guidelines the P2Y12 receptor inhibitor, ticagrelor or prasugrel is recommended over clopidogrel for patients with acute coronary syndrome (ACS). Aims: To determine the effectiveness and safety of Prasugrel versus ticagrelor in patients with ACS/AMI (acute myocardial infarction) who underwent percutaneous coronary intervention (PCI) through meta-analysis of clinical trials. Methods: We performed a meta-analysis of randomized and non-randomized trials [with search results up to April 2023 in the following databases: PubMed (MEDLINE) and Google Scholar comparing prasugrel and ticagrelor in PCI-treated acute ACS/AMI patients for the following: Composite of 1-year all-cause death, non-fatal MI, or stroke; Composite of 1-year cardiovascular death, non-fatal MI, or stroke; and individual parameters (all-cause death, cardiovascular death, non-fatal MI and stroke) and major bleeding as Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding (more severe bleeding) at 1-year. 4 studies met the metanalysis inclusion criteria. It was conducted on the data of a total of 10479 patients (5079 in the prasugrel group and 5400 ticagrelor group). Results: Prasugrel and ticagrelor have insignificant differences for the pooled relative risks of the following: composite of 1-year all-cause death, non-fatal myocardial infarction (MI), or stroke 0.921 (95% CI, 0.719 to 1.181; p =0.518); composite of 1-year cardiovascular death, non-fatal MI, or stroke 0.830 (95% CI, 0.598 to 1.152; p =0.265); BARC type 3 to 5 bleeding (more severe bleeding) at 1-year was 0.988 (95% CI, 0.774 to 1.262; p =0.924); individual parameters (all-cause death, cardiovascular death, non-fatal myocardial infarction (MI) and stroke). There was either inconsistency/heterogeneity and minimal or no inconsistency/heterogeneity for different parameters in the data. There was no publication bias for all trials. Conclusion: Prasugrel and ticagrelor have similar effects for their relative risks of the following; composite of 1-year all-cause death, non-fatal MI, or stroke; composite of 1-year cardiovascular death, non-fatal MI, or stroke; and individual parameters and BARC type 3 to 5 bleeding at 1 year in patients with ACS/AMI undergoing PCI.