The CURRENT-OASIS 7 (Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events–Seventh Organization to Assess Strategies in Ischemic Symptoms) trial showed that a 7-day 150-mg maintenance dose (MD) clopidogrel could reduce cardiovascular events in subgroup patients who underwent percutaneous coronary intervention (PCI) compared with the 75 mg/day regimen, although whether prolonging the high MD clopidogrel (≥150 mg) treatment period to at least 4 weeks can reduce major adverse cardiac events in the patients who underwent PCI with and without high on-clopidogrel platelet reactivity (HPR) is still controversial. We searched Pubmed, Embase, and Cochrane Library from inception until September 2014 for randomized controlled trials that compared high versus standard MD clopidogrel in patients who underwent PCI. Seventeen trials involving 4,822 patients who underwent PCI included 2,879 patients who were allocated to the “HPR patients” subgroup and 1,943 to the “native patients” subgroup without paying attention to the clopidogrel reactivity before randomization. Compared with the standard therapy, the high MD clopidogrel was associated with a significant reduction in the risk of major adverse cardiac events (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.39 to 0.71, p <0.0001) in patients who underwent PCI. The HPR patients subgroup was also benefited from such high MD treatment (OR 0.54, 95% CI 0.38 to 0.77, p = 0.0007). The observed benefits were mainly attributed to treatment-associated reduction in stent thrombosis (OR 0.43, 95% CI 0.23 to 0.78, p = 0.006) and target vessel revascularization (OR 0.38, 95% CI 0.20 to 0.74, p = 0.004). There was no difference in the rate of major/minor bleeding event between the high and standard MD group (OR 0.80, 95% CI 0.56 to 1.13, p = 0.21). In conclusion, the efficacy and safety of at least 4 weeks' high MD clopidogrel is greater than that of standard therapy for patients who underwent PCI with and without HPR.