Recent studies of drug-eluting stents (DES) use in routine clinical practice have led to concern regarding their long-term safety and to questions about the adequacy of current antiplatelet therapy guidelines. This study sought to derivate a risk score for predicting stent thrombosis after drug-eluting stenting. The large single center DES Real-world Incremental Value in the erA of percutaneous revascularizaTION (DERIVATION) database, collecting data about 1,377 patients of any age undergoing PCI with DES as treatment for symptomatic coronary artery disease, was use for this purpose. Logistic regression and bootstrap procedure were used to select correlates of stent thrombosis that were subsequently weighted and integrated into an integer scoring system. Five variables selected from the initial multivariate model were weighted proportionally to their respective odds ratio for stent thrombosis [baseline left ventricular ejection fraction <50% (4 points), angioplasty in the setting of acute coronary syndromes (3 points), bifurcation lesion (2 points), left anterior descending as target vessel (2 points), multiple stenting (2 points)]. Three strata of risk were defined (low risk, 0–2; intermediate risk, 3–6; high risk ≥7) with good prognostic accuracy for early, late and very late thrombosis (c statistic = 0.75, 0.65 and 0.73, respectively) in the derivation set. In conclusion, the DERIVATION score may be used as a simple clinical tool for the identification of a sizable cohort in whom close monitoring and aggressive therapy may be beneficial.