Background Sirolimus-eluting stent (SES) and paclitaxel-eluting stents (PES) have different drug-release kinetics and polymers with different delivery systems; therefore, different patterns of in-stent restenosis (ISR) might be expected. The objectives of this study were to compare the angiographic patterns of ISR between the SES group and the PES group and to compare six months clinical outcomes. Methods This was an observational retrospective study including consecutive symptomatic patients (n=842) assigned to the SES group (n=557) and the PES group (n=285). Patients with previously untreated de novo atherosclerotic lesions were included in this study. Angiographic follow-up was scheduled at six months post-procedure, and Mehran classification was used for description of ISR patterns. Results Baseline patient characteristics were similar in both groups. During the six-month follow-up period, 9.3% (n=52) in the SES group and 17.9% (n=51) in the PES group developed ISR (Table 1). Major adverse cardiac events (death, myocardial infarction, and the need for repeated target lesion revascularization) were 6.5% (n=36) in the SES group and 8.4% (n=24) in the PES group (p=0.296). Conclusion Different pharmacokinetics of drugs and polymers used for coating the stents may have contributed to the different angiographic patterns of ISR between two groups. Although the different angiographic patterns of ISR were observed, six months clinical outcomes were similar between two groups.