Background: In patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with thrombus aspiration, the histopathology of aspirated thrombus was previously related to long‐term mortality. In this study, we sought to investigate the association between histopathology of aspirated thrombus and ST‐segment recovery, a marker of microvascular dysfunction, immediately at the end of the PCI procedure. Methods: We included 892 STEMI patients who underwent primary PCI with routine thrombus aspiration and for whom combined data on histopathology of aspirated thrombus and ST‐segment recovery were available. Patients were categorized according to histopathology of aspirated thrombus: fresh only (<1 day), older (>1 day), or no material aspirated. ST‐segment recovery was defined as incomplete if <50%. Results: Incomplete ST‐segment recovery occurred in 134 of 363 patients (37%) with fresh thrombus, in 104 of 238 patients (44%) with older thrombus, and in 142 of 291 patients (49%) with no material. Unadjusted odds ratios for incomplete ST‐segment recovery of patients with older thrombus and no material, when compared with patients with fresh thrombus, were 1.33 (95% CI, 0.95–1.85; P = 0.097) and 1.63 (95% CI 1.19–2.23; P = 0.002), respectively. Both associations were unchanged after multivariable adjustment for clinical predictors of ST‐segment recovery. ST‐segment recovery was a strong predictor of long‐term mortality, independent of the histopathology of aspirated thrombus. Conclusions: This study shows that ST‐segment recovery immediately at the end of the PCI procedure was a significant prognosticator, independent of the histopathology of aspirated thrombus. We found that the histopathology of aspirated thrombus (fresh, older, no material) was associated with ST‐segment recovery in STEMI patients undergoing primary PCI with thrombus aspiration. © 2010 Wiley‐Liss, Inc.