Background: Protection of distal embolization and thrombus aspiration may improve microvascular circulation and thus decrease myocardial injury during primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI). Randomized trials of distal protection devices during PCI have provided conflicting results in contrast to simple thrombus aspiration. In a prospective randomized trial, we studied the effect of distal protection and thrombus aspiration (DP-TA) in 126 patients with STEMI. Methods: Patients with first-diagnosed STEMI were randomly assigned to DP-TA pretreatment or conventional PCI (c-PCI). Primary end point was microvascular occlusion index (MVO) measured by magnetic resonance imaging (MRI) within 3 days after PCI. Secondary end points were peak CK-MB during hospitalization and infarct size and ejection fraction measured by MRI at post-PCI and 6 months after PCI. Results: Baseline characteristics of the patients including cardiovascular risk factors and lesion characteristics were similar between the two groups. MVO graded by negative, 1, 2 and 3 was not statistically different in the DP-TA group and c-PCI (p=0.806 by Pearson Chi-square). Mean peak CK-MB was 398짹36 in DP-TA group and 424짹35.7 in c-PCI group (p=0.618). Initial and 6-month infarct size and ejection fraction was also similar [infarct area% (DP-TA vs c-PCI): initial 29.0짹2.0 vs 29.6짹2.0  6 months 24.7짹2.0 vs 22.2짹1.6, EF: initial 56.3짹1.7 vs 53.8짹1.73  56.8짹1.9 vs 56.7짹2.3]. In subgroup analyses, infarct territory or lesion proximity did not affect the results. Conclusion: DP-TA did not show a benefit in primary PCI for STEMI in MVO as well as infarct size. This study suggests a possible difference between simple thrombus aspiration and DP-TA in STEMI.