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To evaluate the predictive value of Type D personality on in-stent restenosis (ISR) rates at 1 and 2 years post–percutaneous coronary intervention (PCI) in patients with coronary artery disease.Consecutive patients with coronary artery disease who underwent PCI for drug-eluting stents (n = 173) completed the Type D Scale-14 (DS14) at baseline. Follow-up coronary angiographic evaluation was routinely planned at 1 and 2 years after the procedure.Follow-up coronary angiography was performed in 159 and 112 patients at 1 and 2 years post-PCI, respectively. On multivariate analysis, Type D personality was found to be an independent predictor of ISR at 1 year (odds ratio [OR] = 2.67, 95% confidence interval [CI] = 1.16–6.14, p = .021) and 2 years (OR = 4.92, 95% CI = 1.82–9.60, p = .017) after adjusting for cardiovascular risk factors. However, Type D did not predict ISR when the analysis was performed using the interaction between negative affectivity and social inhibition. The main effect of negative affectivity emerged as a significant risk factor for 1-years (OR = 4.22, 95% CI = 1.18–7.86, p = .034) and 2-year ISR (OR = 6.93, 95% CI = 2.25–11.50, p = .016).In this study, Type D personality was an independent predictor of ISR at 1 and 2 years post-PCI; the association strengthened with time. The negative affectivity component seems to drive the relationship between Type D and ISR over time. Our findings provide new insights into the mechanisms involved in the association between Type D and adverse clinical outcomes of PCI.