The study aimed to compare the efficacy and safety outcome associated with a short and a prolonged duration of thienopyridine therapy in patients with chronic kidney disease (CKD) after coronary stenting. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 January 2019 for studies comparing short and prolonged thienopyridine therapy in patients with CKD. Ischemic and bleeding events were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Seven studies comprising a total of 17,628 CKD patients were included in the evaluation. Prolonged duration of thienopyridine use, when compared to short-term thienopyridine, was associated with reduced risk of all-cause mortality (odds ratio 0.75, 95% confidence interval: 0.70-0.81, P< .001) and stent thrombosis (OR: 0.54, 95% CI 0.32 to 0.89; P< .001), but the odds of myocardial infarction (OR: 0.91, 95% CI: 0.77-1.07; P = .23) and stroke (OR: 0.91, 95% CI 0.73 to 1.13; P = .38) did not differ according to different duration of thienopyridine. As for bleeding events, long-term thienopyridine therapy did not significantly increase the bleeding (OR: 0.95, 95% CI 0.79 to 1.14; P = .58). In these patients with CKD following PCI, prolonged thienopyridine therapy compared with short-term therapy, was associated with reduced all-cause mortality and stent thrombosis, without any significant difference in myocardial infarction, stroke, and bleeding. Thienopyridine prolongation decisions for CKD patients should be individualized after careful consideration of the benefit-risk balance.