Introduction: Recent American Heart Association/American College of Cardiology guidelines on duration of dual antiplatelet therapy (DAPT) recommend DAPT for 12 months in patients presenting with an acute coronary syndrome (ACS) who underwent percutaneous intervention (PCI) (grade IIb recommendation). With the advent of newer generation stents, multiple randomized controlled trials (RCTs) have studied the role of short term -3 months DAPT compared to the guideline-indicated12 months DAPT. We aim to assess the evidence using a meta-analytic approach. Methods: PubMed, Embase and Cochrane Central databases were searched from inception until May 31, 2021. RCTs comparing short term (3 months) vs extended (12 months) DAPT in patients with ACS undergoing PCI were included. Outcomes assessed were MACE, cardiovascular mortality, all-cause mortality, myocardial infarction, stent thrombosis and bleeding events. A random-effects model was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI). Results: We included 5 trials comprising 16,781 patients with an acute coronary syndrome that underwent percutaneous intervention. There was no significant difference in MACE (RR 0.92; 95% CI, 0.76-1.11), cardiovascular mortality (RR 1.26; 95% CI, 0.38-4.17), or all-cause mortality (RR 0.92; 95% CI, 0.48-1.77) between the 2 groups. In addition, there was no difference in rates of myocardial infarction (RR 0.98; 95% CI, 0.74-1.30), or stent thrombosis (RR 1.30; 95% CI, 0.55-3.05) between short-term and extended DAPT. However, compared with extended DAPT, 3-month DAPT showed significantly reduced risk of major bleeding (RR 0.53; 95% CI, 0.43-0.64). Conclusions: In patients with acute coronary syndrome undergoing PCI, short term DAPT may be reasonable for some patients, while extended DAPT may be appropriate for select others. An individualized approach on optimal DAPT duration should be used considering the risks of ischemic events and bleeding.