In response to findings from small trials, and subsequent changes to practice guidelines, manual thrombectomy is increasingly being performed before stent deployment in the setting of primary percutaneous coronary intervention (PCI). However, a meta-analysis published in 2010 indicated the possibility of an increased risk of stroke with thrombectomy, and a later trial found no mortality benefit with the procedure. In TOTAL, 10,732 patients with STEMI were randomly assigned to primary PCI with or without upfront manual aspiration thrombectomy. The primary outcome—death from a cardiovascular cause, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days—did not differ between the two treatment groups. However, stroke within 30 days—the key safety outcome—was more likely with thrombectomy + PCI than with PCI alone (0.7% vs 0.3%; HR 2.06, 95% CI 1.13–3.75; P = 0.02).