Objectives The authors sought to investigate the impact of distal embolization (DE) on myocardial damage and microvascular reperfusion, according to time-to-treatment, using contrast-enhanced cardiac magnetic resonance (CE-CMR). Background DE, occurring during primary percutaneous coronary intervention (p-PCI), appears to increase myocardial necrosis and to worsen microvascular perfusion, as shown by surrogate markers. However, data regarding the behavior of DE on jeopardized myocardium, and in particular on necrosis extent and distribution, are still lacking. Methods In 288 patients who underwent p-PCI within 6 h from symptom onset, the authors prospectively assessed the impact of DE on infarct size and microvascular damage, using CE-CMR. The impact of DE was assessed according to time-to-treatment: for group 1, <3 h; for group 2, ≥3 and ≤6 h. Results DE occurred in 41 (14.3%) patients. Baseline clinical characteristics were not different between the 2 groups. At CE-CMR, patients with DE showed larger infarct size (p = 0.038) and more often transmural necrosis compared with patients without DE (p = 0.008) when time-to-treatment was <3 h, but no impact was proven after this time (p = NS). Patients with DE showed more often microvascular obstruction, as evaluated at first-pass enhancement, than patients without DE (100% vs. 66.5%, p = 0.001) up to 6 h from symptom onset. Conclusions These findings suggest that the detrimental impact of DE occurring during p-PCI on myocardial damage is largely influenced by ischemic time, increasing the extent of necrosis in patients presenting within the first hours after symptom onset, and having limited or no impact after this time window.