The Florence Acute Myocardial Infarction registry was a population-based, prospective study aimed at identifying the determinants of coronary reperfusion therapy [CRT, by primary coronary intervention (PCI) in more than 95% of cases] utilization and of prognosis in patients with ST-segment elevation myocardial infarction (STEMI). The registry involved one teaching hospital with, and five district hospitals without PCI facilities. Overall, as many as 45.6% of 930 cases of STEMI did not receive any form of CRT. In multivariable analysis, the direct admission to the teaching hospital was the strongest positive predictor, whereas the time delay, older age, and chronic comorbid conditions were negative predictors of CRT utilization. Compared to conservative therapy, CRT was associated with a remarkably reduced 12-month mortality, after adjusting for age, chronic comorbidities and Killip class, which also were significantly associated with long-term prognosis. The higher crude mortality observed in women was accounted for by older age and other age-related factors. The improvement in prognosis with CRT was larger in older patients and/or in those with a greater burden of chronic comorbidity, who less frequently received CRT. These results suggest the need for interdisciplinary reassessing the adherence to therapeutic guidelines and the criteria adopted in the real clinical world to select patients for CRT during STEMI.