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Background: In-stent restenosis remains an unresolved issue. Inflammation plays a pivotal role in the process of in-stent restenosis. Significant and positive associations were found between red blood cell distribution width (RDW) and inflammation. But whether there is a close relationship between higher RDW and in-stent restenosis is still not clarified., Methods: This retrospective observational study investigated 214 consecutive patients with unstable angina pectoris who underwent successful percutaneous coronary interventions with drug-eluting stents. Patients were divided into three groups according to baseline RDW before percutaneous coronary interventions (low RDW group:≤12.5%; intermediate RDW group:> 12.5% and ≤ 13.5%; high RDW group:> 13.5%). The follow-up angiographies were routinely performed 9-12 months after the initial percutaneous coronary interventions. The multivariate logistic regression analysis was employed to determine the independent predictors of in-stent restenosis., Results: The in-stent restenosis rate was significantly higher in group with higher baseline RDW value (12.3, 19.7, 47.7% in low, intermediate, and high RDW groups respectively, P < 0.001). The baseline RDWs were significantly higher in patients with in-stent restenosis compared with those in patients without in-stent restenosis (13.7 ± 0.8% vs. 13.0 ± 0.8%, P < 0.001). For prediction of in-stent restenosis, the ROC (receiver operating characteristic) curve analysis demonstrated the optimal RDW cutoff value was 13.37 (sensitivity: 65.5%, specificity: 73.6%); the diagnosis cutoff value was 13.89 (sensitivity: 40.0%, specificity: 91.8%); the screening cutoff value was 12.99 (sensitivity: 83.6%, specificity: 49.1%). By multivariate logistic analysis, higher baseline RDW (odds ratio [OR], 5.179; 95% confidence interval [CI], 2.568 to 10.446; P<0.001) together with lower baseline indirect bilirubin (OR, 0.413; 95% CI, 0.305 to 0.559; P<0.001) and diabetes (OR, 4.077; 95% CI, 1.654 to 10.054; P = 0.002) were closely associated with in-stent restenosis at followup (11.1 ± 5.8 months)., Conclusions: The baseline RDW was closely associated with in-stent restenosis at follow-up. The patients with higher baseline RDW might have more chances to develop in-stent restenosis at followup.