Background The clinical impact of early aspirin discontinuation compared with dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention with stenting remains poorly studied. We investigated the clinical outcomes of patients assigned to either early aspirin discontinuation or DAPT after percutaneous coronary intervention with stenting. Methods and Results We performed a meta-analysis of aggregate data from randomized clinical trials enrolling participants receiving a percutaneous coronary intervention with stenting and assigned to either early aspirin discontinuation or DAPT. Scientific databases were searched from inception through March 30, 2020. Trial-level hazard ratios (HRs) and 95% CIs were pooled using a random effects model with inverse variance weighting. The primary outcome was all-cause death. Secondary outcomes were myocardial infarction, stent thrombosis, stroke, and major bleeding. Overall, 36 206 participants were allocated to either early aspirin discontinuation (experimental therapy, n=18 088) or DAPT (control therapy, n=18 118) in 7 trials. Median follow-up was 12 months. All-cause death occurred in 2.5% of patients assigned to experimental and 2.9% of patients assigned control therapy (hazard ratio [HR], 0.91, 95% CI, 0.75-1.11; P=0.37). Overall, patients treated with experimental versus control therapy showed no significant difference in terms of myocardial infarction (HR, 1.02 [0.85-1.22], P=0.81), stent thrombosis (HR, 1.02 [0.87-1.20], P=0.83), or stroke (HR, 1.01 [0.68-1.49], P=0.96). However, the risk for major bleeding (HR, 0.58 [0.43-0.77], P<0.01) was significantly reduced by experimental as compared with control therapy. Conclusions In patients treated with percutaneous coronary intervention and stenting, assigned to a strategy of early aspirin discontinuation versus DAPT, the risk of death and ischemic events is not significantly different but the risk of bleeding is lower.