No data exist regarding the relationship between aspirin/clopidogrel resistance and intra-stent thrombi on follow-up optical coherence tomography (OCT) after drug-eluting stent (DES) implantation. The purpose of this study was to evaluate the relationship between aspirin/clopidogrel resistance and intra-stent thrombi on the follow-up OCT in DES-treated patients. A total of 308 DES-treated patients who underwent follow-up OCT and simultaneous measurement of aspirin reaction unit (ARU) and P2Y12 reaction unit (PRU) using the VerifyNow assay system were selected for the study. Aspirin and clopidogrel resistance were defined as ARU ≥550 and PRU ≥275, respectively. Intra-stent thrombi were detected in 29 patients (9.4%). The mean time interval from DES implantation to OCT was 195 ± 133 days (202.9 ± 103.0 days for patients with intra-stent thrombi vs. 194.7 ± 136.0 days for patients without intra-stent thrombi; P = 0.750). There were no significant differences between patients with and without intra-stent thrombi with regard to the incidence of aspirin resistance (13.8 vs. 11.1%, respectively; P = 0.630) or clopidogrel resistance (72.4 vs. 50.5%, respectively; P = 0.056). The percentage of uncovered struts was 17.9 ± 15.8% in patients with intra-stent thrombi and 12.7 ± 17.3% in patients without intra-stent thrombi (P = 0.098). Stent length was significantly longer in patients with intra-stent thrombi (22.9 ± 6.0 vs. 19.4 ± 5.0 mm, P = 0.006). Multivariate logistic regression analysis showed that stent length (odds ratio = 1.152, 95% confidential interval 1.025-1.295; P = 0.017) was the only independent risk factor for the presence of intra-stent thrombi on OCT. This OCT study suggested that the presence of intra-stent thrombi may not be associated with aspirin/clopidogrel resistance in DES-treated patients.