In this study, we aimed to evaluate the utility of the immune-inflammation index (SII) in estimating the no-reflow phenomenon and short-term cardiovascular prognosis in patients with ST-segment elevation myocardial infarction (STEMI). 723 consecutive patients with STEMI who underwent primary percutaneous coronary intervention (PCI) were enrolled in our study. The receiver-operating characteristics (ROC) curve was used to determine the cut-off value of SII to predict the no-reflow. The multivariate regression analysis analyzed the correlation between no-reflow and SII. The median value of SII was significantly higher in patients with no-reflow in comparison with normal reperfusion [1466 (939–2409) vs 905 (566–1379), p < .001]. The optimal threshold for SII in predicting the no-reflow phenomenon was 1036, with sensitivity and specificity of 70% and 59%, respectively. The area under the ROC curve (AUC) was 0.71 (95% CI, 0.66–0.75, p < .001). In multivariate analysis, SII ≥ 1036 value showed an independent predictive value for the no-reflow (OR = 0.51, 95% CI: 0.29–0.92, p = .02) and the 30-day cardiovascular mortality (OR = 2.37, 95% CI: 1.34–4.19, p = .003). Our results suggest that higher SII levels are independently associated with the no-reflow phenomenon and 30-day mortality in STEMI patients undergoing primary PCI.