The angiographic features of restenosis contain prognostic information. However, restenosis patterns of the new generation drug-eluting stents (DES), everolimus-(EES) and resolute zotarolimus-eluting stent (ZES) have not been described.A total of 210 consecutive patients with DES restenosis were enrolled from 2003 to 2012. We analyzed 217 restenotic lesions after DES implantation, and compared the morphologic characteristics of the 2nd generation DES restenosis to those of restenosis with 2 first generation DES, sirolimus-(SES) and paclitaxel-eluting stent (PES).Baseline characteristics were comparable between the different stent groups. The incidence of focal restenosis was significantly lower for PES than the other stents (49.5% versus 87.0%, 76.2%, and 82.1% for PES versus SES, EES, and ZES, respectively, P < 0.001). When considering the pattern of restenosis solely within the stent margins, a further clear distinction between PES and other stents was observed (40.0% versus 92.9%, 88.9%, and 81.2% in PES versus SES, EES, and ZES, respectively, P < 0.001). There were no significant differences in restenosis patterns among SES, EES, and ZES. In multivariate analysis, PES implantation, hypertension, and age were associated with non-focal type of restenosis after DES implantation. After the introduction of EES and ZES into routine clinical practice in 2008, focal restenosis significantly increased from 63.9% to 76.7% and diffuse restenosis significantly decreased from 26.4% to 11.0% (P = 0.045).Focal restenosis was the most common pattern of restenosis in the new generation DES and the incidence of diffuse restenosis significantly decreased with the introduction of the 2nd generation DES.