Background and objectives: We aimed to demonstrate the clinical utility of CHA2DS2-VASc score in risk assessment of patients with STEMI regarding adverse clinical outcomes particularly no-reflow phenomenon. Materials and Methods: We designed a retrospective cohort study using the data of Tehran Heart Center registry for acute coronary syndrome. The study included 1331 consecutive patients with STEMI who underwent primary angioplasty. Patients were divided into two groups according to low and high CHA2DS2-VASc score. Angiographic results of reperfusion were inspected to evaluate the association of high CHA2DS2-VASc score and the likelihood of suboptimal TIMI flow. The secondary endpoint of the study was short-term in-hospital mortality of all cause. Results: The present study confirmed that CHA2DS2-VASc model enables us to determine the risk of no-reflow and all-cause in-hospital mortality independently. Odds ratios were 1.59 (1.30–2.25) and 1.60 (1.17–2.19), respectively. Moreover, BMI, high thrombus grade, and cardiogenic shock were predictors of failed reperfusion (odds were 1.07 (1.01–1.35), 1.59 (1.28–1.76), and 8.65 (3.76–24.46), respectively). We showed that using a cut off value of ≥ two in CHA2DS2-VASc model provides a sensitivity of 69.7% and specificity of 64.4% for discrimination of increased mortality hazards. Area under the curve: 0.72 with 95% CI (0.62–0.81). Conclusions: Calculation of CHA2DS2-VASc score applied as a simple risk stratification tool before primary PCI affords great predictive power. Furthermore, incremental values are obtained by using both CHA2DS2-VASc and no-reflow regarding mortality risk assessment.