Purpose: There is a lack of sufficient data in comparison of optical coherence tomographic (OCT) findings between first- and second-generation drug-eluting stents (DES). Compared to first-generation (i.e., sirolimus- or paclitaxel-eluting stents), second-generation DESs (i.e., everolimus- or biolinx-based zotarolimus-eluting stents) might have more favorable neointimal coverage. Materials and Methods: Follow-up OCT findings of 103 patients (119 lesions) treated with second-generation DESs were compared with those of 139 patients (149 lesions) treated with first-generation DESs. The percentage of uncovered or malapposed struts, calculated as the ratio of uncovered or malapposed struts to total struts in all OCT cross-sections, respectively, was compared between the two groups. Results: Both DES groups showed similar suppression of neointimal hyperplasia (NIH) on OCT (mean NIH cross-sectional area; second- vs. first-generation=1.1 +/- 0.5 versus 1.2 +/- 1.0 mm(2), respectively, p=0.547). However, the percentage of uncovered struts of second-generation DESs was significantly smaller than that of first-generation DESs (3.8 +/- 4.8% vs. 7.5 +/- 11.1%, respectively, p<0.001). The percentage of malapposed struts was also significantly smaller in second-generation DESs than in first-generation DESs (0.4 +/- 1.6% vs.1.4 +/- 3.7%, respectively, p=0.005). In addition, intra-stent thrombi were less frequently detected in second-generations DESs than in first-generation DESs (8% vs. 20%, respectively, p=0.004). Conclusion: This follow-up OCT study showed that second-generation DESs characteristically had greater neointimal coverage than first-generation DESs.