Due to recent advances in stent design, stenting without balloon predilation (direct stenting) has become more extensively used in patients with acute myocardial infarction (AMI). We performed a randomized study with broad inclusion criteria and early randomization after presentation to compare direct stenting with stenting after balloon predilation in patients with AMI. A total of 248 patients was randomized. After exclusion of patients not suitable for stenting, the final study group comprised 217 patients. Direct stenting strategy was feasible in 88% of patients with no meaningful complications. Final Thrombolysis In Myocardial Infarction grade 3 flow (96% vs 94%), final Thrombolysis In Myocardial Infarction myocardial perfusion grade 2 or 3 (68% vs 61%), and average ST-segment resolution after the procedure (49% vs 51%) were similar in the direct stenting and predilation groups, respectively (p = NS). Rate of in-stent restenosis was higher in the direct stenting group (30% vs 16%, p = 0.024), which was due to a worse angiographic result after the procedure. At 5 years, a composite of cardiac death, reinfarction, and target lesion revascularization had occurred in 39% in the direct stenting group and 34% in the predilated group (p = 0.40). In conclusion, although at 5 years clinical outcome did not differ significantly between groups, direct stenting was associated with a higher incidence of in-stent restenosis at 1 year. Direct stenting did not improve epicardial and myocardial reperfusion indexes. Direct stenting strategy should not be recommended in all patients with AMI as an alternative strategy to stenting after predilation.