OBJECTIVES: The purpose of this study was to evaluate the effectiveness of combined proximal embolic protection with thrombus aspiration (Proxis Embolic Protection System [St. Jude Medical, St. Paul, Minnesota]) in ST-segment elevation myocardial infarction patients. BACKGROUND: Embolization during primary percutaneous coronary intervention (PCI) may result in microvascular obstruction, reduced myocardial perfusion, and impaired prognosis. METHODS: Two hundred eight-four patients were randomized to primary PCI with the Proxis system versus primary PCI alone after angiography. The primary end point was the occurrence of complete (> or =70%) ST-segment resolution (STR) at 60 min measured by continuous ST-segment Holter. RESULTS: There was no significant difference in the occurrence of the primary end point (80% vs. 72%, p = 0.14). However, immediate complete STR (at time of last contrast) occurred in 66% of Proxis-treated patients and 50% in control patients (absolute difference, 16.3%; 95% confidence interval: 4.3% to 28.2%; p = 0.009). A significant lower ST-segment curve area (0 to 3 h after primary PCI) was observed in the Proxis arm (5,192 microV/min vs. 6,250 microV/min, p = 0.037). Major adverse cardiac and cerebral events at 30 days occurred with similar frequency in both groups (6 vs. 10). CONCLUSIONS: There was no significant difference in complete STR at 60 min in this proof-of-concept study. However, we observed a significant difference in immediate complete STR in Proxis-treated patients, better STR at later time points, and a reduction of electrocardiogram injury current over time, compared with control patients. The results suggest that primary PCI with the Proxis system may lead to better immediate microvascular flow in ST-segment elevation myocardial infarction patients. (The PREPARE Study; ISRCTN71104460).