Abstract Incomplete ST segment resolution (iSTR) is a well-known marker of poor outcome in patients undergoing primary percutaneous coronary intervention (pPCI) for ST elevation myocardial infarction (STEMI). The use of glycoprotein IIbIIIa inhibitors (GPIs) was suggested to be associated with a survival benefit in high-risk patients. A simple score to predict the risk for developing iSTR could help early identification of these patients and could allow a tailored use of pharmacological tools, such as GPIs. The aim of this study was to create and validate a numerical score to predict iSTR occurrence in STEMI patients undergoing pPCI and to assess its association with the potential benefit of GPIs use. We prospectively enrolled all STEMI patients undergoing pPCI in our University Hospital (2005–2017). iSTR was defined as a <70% resolution of initial ST segment shift in the lead with maximal ST deviation 60 min after reperfusion. Our population was randomly divided in two group: a derivation cohort (60%) and a validation cohort (40%). Potential predictors of iSTR were selected at univariate analysis and were then inserted in a multivariate binary stepwise-backward logistic regression. To create a risk score, numerical values were obtained considering the odds ratio of each independent predictor rounding to the nearest unit or half. A ROC curve with its c-statistic was then used to test the discrimination power of the score both in the derivation and in the validation cohort. Out of a total of 2959 patients, 1774 were included in the derivation: 480 (27%) of them presented iSTR. All-cause mortality at 30 days was significantly higher in patients with iSTR (OR 3.2, 95% CI 2.1–4.9, p<0.001). Anterior MI (OR 2.46, 95% CI 1.90–3.14, p<0.001, score 2.5), anemia at admission (OR 1.76, 95% CI 1.29–2.4, p<0.001, score 2), blood glucose >198 mg/dl at admission (OR 1.77, 95% CI 1.29–2.49, p<0.001, score 2), age >75 years (OR 1.54, 95% CI 1.15–2.10, p=0.004, score 1.5), female sex (OR 1.41, 95% CI 1.06–1.88, p=0.02, score 1.5) and Killip class >2 (OR 1.44, 95% CI 1.05–1.98, p=0.024, score 1.5) were identified as independent predictors of iSTR, creating a ISTR-score that ranged from 0 to 11. The validation cohort consisted in 1185 patients, with 31% showing iSTR. The c-statistic was 0.67 and 0.66 in the derivation and validation cohorts. Patients with score ≥4 versus <4 showed present a worst prognosys but a similar GPI use. Notably, GPIs were associated with a significant survival benefit among patients≥4 but not among patients <4 (Figure). The use of GPIs was not associated to any clinically relevant difference, the increase in bleeding risk appeared similar. A simple pre-procedural risk score may predict iSTR following pPPCI, allowing a rapid risk stratification and the identification of patients who show a favorable risk/benefit ratio for the use of more aggressive strategies such as GPIs. These findings deserve a prospective, randomized evaluation.