AIMS: We aimed to determine the efficacy and safety of different anti-platelet regimens after percutaneous coronary intervention (PCI) with drug eluting stent (DES) implantation using a network meta-analysis of randomized controlled trials (RCTs). METHODS: RCTs comparing shorter duration (≤6 months) of dual antiplatelet therapy (S-DAPT) with either aspirin (ASA) or P2Y12 inhibitor monotherapy against longer duration (≥12 months) DAPT (L-DAPT) after PCI were searched in the MEDLINE, EMBASE and COCHRANE databases. End-points of interest were all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stent thrombosis (ST), major bleeding and major or minor bleeding. Network meta-analyses were performed using frequentist approach. RESULTS: Eighteen RCTs with total of 57,942 patients met the inclusion and exclusion criteria. This included 14 RCTs (N = 28,853) of S-DAPT with ASA monotherapy and 4 RCTs (N = 29,089) with P2Y12 inhibitor monotherapy. Compared with L-DAPT, the odds of MI were higher with S-DAPT with ASA monotherapy [OR 1.23; 95% CI 1.01-1.48], but not with P2Y12 inhibitor monotherapy [0.98; 0.85-1.14]. Both S-DAPT regimens lowered rates of major bleeding when compared with L-DAPT; ASA monotherapy [0.70; 0.49-1.00] and P2Y12 monotherapy [0.67; 0.45-0.98]. There were no differences in risks of all-cause or CV death between either regimen of S-DAPT and L-DAPT. However, in the acute coronary syndrome subgroup, ASA monotherapy was associated with increased risk of ST [1.55; 1.021-2.36] but P2Y12 monotherapy was not [0.93; 0.58-1.48]. CONCLUSION: Amongst patients undergoing DES implantation, S-DAPT with P2Y12 inhibitor monotherapy reduces bleeding without increased risk of MI or ST compared with L-DAPT. Prospective trials are needed to evaluate if S-DAPT with P2Y12 monotherapy is superior to S-DAPT with ASA monotherapy for ischemic protection.