Abstract Background Increased platelet indices have been shown to reflect higher degree of platelet activation and have been related to poorer short- and long-term outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). Purpose We aimed to evaluate the ability of a validated marker of platelet activation (i.e., the platelet-large cell ratio [P-LCR]) to predict the occurrence of no-reflow in patients undergoing primary percutaneous coronary intervention (pPCI) for STEMI. The ability of P-LCR to predict other markers of thrombotic charge (i.e., use of glycoprotein IIb/IIIa inhibitors and/or thrombus aspiration) was also investigated. Methods Use of glycoprotein IIb/IIIa inhibitors and/or thrombus aspiration, occurrence of the ‘no-reflow’ phenomenon and P-LCR values on admission were recorded in 836 consecutive patients treated by pPCI for STEMI. Patients’ demographic data and symptom onset-to-cardiac catheterization laboratory time intervals were also recorded. Correlations between P-LCR values and the presence of thrombotic charge markers were evaluated. Results No-reflow occurred in 124 (14.8%) of the study patients; glycoprotein IIb/IIIa inhibitors and thrombus aspiration were used in 228 (27.3%) and in 289 (34.5%) of patients, respectively. Mean P-LCR values were 27.1 ± 7.6%. P-LCR values on admission were significantly higher in patients who presented no-reflow than in those who did not (29.1 ± 5.6% vs. 25.3 ± 5.8%, p = 0.03). Similarly, P-LCR were significantly higher in patients in whom glycoprotein IIb/IIIa inhibitors (29.5 ± 6.1% vs. 25.2 ± 5.3%, p = 0.04) and/or thrombus aspiration (28.4 ± 5.7% vs. 24.8 ± 5.4%, p = 0.03) were used. A P-LCR value ≥26.9% predicted the occurrence of no-reflow with 70.9% sensitivity and 55.4% specificity (p = 0.04). Conclusions In the present cohort, P-LCR values on admission predicted the presence of thrombotic charge markers in patients undergoing pPCI for STEMI. Evaluating P-LCR on admission could help identify patients at increased risk of no-reflow, in whom more intensive antiplatelet strategies may be of interest.