ObjectiveTo evaluate the long term efficacy and safety of long duration DAPT (L-DAPT) compared to short duration DAPT (S-DAPT) after drug-eluting stent (DES) implantation.; MethodsWe searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the clinical impact of L-DAPT versus S-DAPT after DES and have mean follow up period of at least 2 years or longer. Primary end point was stent thrombosis (ST). Secondary endpoints were all-cause mortality, cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR), thrombolysis in myocardial infarction (TIMI) major bleeding and stroke. Event rates were compared using a random effects model.; ResultsWe identified five RCTs in which 19,760 patients were randomized to S-DAPT (N=9,810) and L-DAPT (n=9,950), respectively. Compared with L-DAPT, S-DAPT was associated with higher rate of MI (odds ratio [OR] 1.48, 95% confidence interval [CI] [1.04, 2.10]). There were no significant differences between S-DAPT and L-DAPT in terms of all cause mortality, cardiac mortality, ST, TVR or stroke (OR 0.90, 95% CI [0.73, 1.12]; OR 1.02, 95% CI [0.80, 1.30]; OR 1.59, 95% CI [0.77, 3.27]; OR 0.87 95% CI [0.67, 1.14]; and OR 1.08 95% CI [0.81, 1.46], respectively). However, rate of TIMI major bleeding was significantly lower with S-DAPT compared to L-DAPT (OR 0.64, 95% CI [0.41, 0.99]).; ConclusionsIn the present analysis of RCTs with longer follow up (2 years or longer), S-DAPT compared with L-DAPT, was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all cause mortality, cardiac mortality, ST, TVR, and stroke.