Background: Up to 24% of patients presenting with ST-elevation myocardial infarction (STEMI) show resolution of ST-elevation and symptoms before revascularization. The mechanisms of spontaneous reperfusion are unclear. Given the more favorable outcome of transient STEMI, it is important to obtain further insights in differential aspects. Methods: We compared 251 patients who presented with transient STEMI (n = 141) or persistent STEMI (n = 110). Clinical angiographic and laboratory data were collected at admission and in subset of patients additional index hemostatic data and at steady-state follow-up. Cardiac magnetic resonance imaging (CMR) was performed at 2–8 days to assess myocardial injury. Results: Transient STEMI patients had more cardiovascular risk factors than STEMI patients, including more arterial disease and higher cholesterol values. Transient STEMI patients showed angiographically more often no intracoronary thrombus (41.1% vs. 2.7%, P < 0.001) and less often a high thrombus burden (9.2% vs. 40.0%, P < 0.001). CMR revealed microvascular obstruction less frequently (4.2% vs. 34.6%, P < 0.001) and smaller infarct size [1.4%; interquartile range (IQR), 0.0–3.7% vs. 8.8%; IQR, 3.9–17.1% of the left ventricle, P < 0.001] with a better preserved left ventricular ejection fraction (57.8 ± 6.7% vs. 52.5 ± 7.6%, P < 0.001). At steady state, fibrinolysis was higher in transient STEMI, as demonstrated with a reduced clot lysis time (89 ± 20% vs. 99 ± 25%, P = 0.03). Conclusions: Transient STEMI is a syndrome with less angiographic thrombus burden and spontaneous infarct artery reperfusion, resulting in less myocardial injury than STEMI. The presence of a more effective fibrinolysis in transient STEMI patients may explain these differences and might provide clues for future treatment of STEMI.