The DAPT score is a recently-proposed decision tool for guiding optimal duration of dual antiplatelet therapy (DAPT). It showed modest accuracy in prior derivation and validation cohorts of patients with ≥12 months DAPT. This study was aimed to evaluate the validity of the DAPT score in a cohort of patients with 6 or 12 months DAPT after implantation of predominantly second-generation drug-eluting stents. We analyzed data of patients enrolled in the ISAR-SAFE trial. Patients were classified into low (<2) or high (≥2) DAPT score groups. Primary ischaemic (all-cause death, myocardial infarction, definite stent thrombosis or stroke) and bleeding (TIMI major or minor) outcomes were analyzed in the low and high DAPT score groups. Data of 3976 patients were available for DAPT score calculation. 2407 patients (60.5%) were classified in the low DAPT score group and 1569 patients (39.5%) in the high DAPT score group. In the low DAPT score group there were no significant differences between 6 and 12 months DAPT regarding ischaemic (1.0% vs. 1.4%, HR=0.74, 95% CI, 0.35–1.57; p=0.43) or bleeding outcomes (0.3% vs. 0.8%, HR=0.44, 95% CI, 0.13–1.42; p=0.17). In the high DAPT score group there were also no significant differences between 6 and 12 months DAPT regarding ischaemic (1.9% vs. 1.8%, HR=1.02, 95% CI, 0.49–2.14; p=0.96) or bleeding (0.3% vs. 0.5%, HR=0.51, 95% CI, 0.09–2.78; p=0.44) outcomes. In conclusion, the DAPT score failed to show a differential treatment effect in patients receiving 6 or 12 months DAPT after contemporary drug-eluting stent implantation.