Objective To explore the long-term clinical efficacy and safety of 6-month dual antiplatelet therapy (DAPT) after biodegradable polymer based drug eluting stent (DES) implantation. Methods In the multi-center prospective CREATE Study, a total of 2034 patients who received biodegradable polymer based sirolimus eluting stent (Excel stent) treatment and had no major adverse cardiac events (MACE) at 6-month were included. Among them, 1626 (79.9%) patients discontinued clopidogrel treatment within 6 months (DAPT≤6 months) and 408 (20.1%) prolonged clopidogrel treatment after 6 months (DAPT＞6 months). The incidences of MACE and stent thrombosis through 6 months to 4 years were compared between patients with different DAPT durations. Results There was no statistical difference between the two groups in the incidences of cardiac death (2.0% vs 2.2%, P=0.753), myocardial infarction (0.2% vs 0.4%, P=1.0), target lesion revascularization (1.7% vs 2.4%, P=0.407) and MACE (3.7% vs 3.4%, P=0.819). The overall incidence of stent thrombosis in patients with DAPT＞6 months and≤6 months was 1.5% and 0.7%, respectively (P=0.128). The incidences of definite or probably stent thrombosis were similar between the two groups (0.7% vs 0.5%, P=0.469). Multivariate analysis showed that prior myocardial infarction was an independent predictor of stent thrombosis (OR=15.313, 95% CI: 4.02?58.25, P＜0.001). However, DAPT duration of ≤6 months was neither associated with the risk of MACE (OR=0.987, 95%CI: 0.545?1.787, P=0.965) nor stent thrombosis (OR=0.847, 95%CI: 0.208?3.439, P=0.816). Conclusions DAPT for 6 months is safe and effective at four years after biodegradable polymer based DES implantation, which needs further confirmation by randomized controlled studies.