In patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), a patent infarct-related artery on initial angiography was associated with better angiographic results and improved prognosis compared with patients without spontaneous reflow. Little is known about the prevalence, clinical course, and optimal management of patients presenting with clinical signs of spontaneous reperfusion (SR). The objective was to evaluate characteristics and clinical outcomes in patients with STEMI with clinical signs of SR. The study included 710 consecutive patients with STEMI eligible for reperfusion therapy who were followed up for 30 days. SR was defined as a ≥70% reduction in sum ST elevation and pain severity before initiation of reperfusion therapy. SR was observed in 155 patients (22%). Although almost all patients with STEMI without SR underwent primary reperfusion using primary PCI (398 of 555 patients; 72%) or thrombolysis (125 of 555; 23%), most patients with SR were initially treated conservatively, and primary PCI was performed in only 13 patients (8%). Although patients with SR had a higher incidence of recurrent in-hospital ischemia, they developed smaller myocardial infarctions and sustained less in-hospital cardiogenic shock, heart failure, and electrical complications and had lower 7- and 30-day mortality rates. On multivariate analysis, SR remained significantly associated with a lower incidence of the combined end point of 30-day mortality, congestive heart failure, and recurrent acute coronary syndrome. In conclusion, despite initial conservative therapy, the outcome of patients with SR was markedly better than for patients without SR who underwent primary reperfusion.