It is unknown if collateral circulation (CC) has a beneficial effect on outcomes of patients who undergo mechanical intervention in the first hours after onset of acute myocardial infarction (AMI). This study analyzes the relation between CC and outcome in patients with AMI who underwent primary angioplasty or stenting within 6 hours of symptom onset. The analysis was performed in a series of 1,164 consecutive patients. The contribution of clinical, angiographic, and procedural variables to the angiographic and clinical outcomes was evaluated by multivariate logistic regression analysis and the Cox proportional hazard model, respectively. Of 1,164 patients, 264 (23%) had angiographic evidence of CC. Patients with CC had a lower incidence of diabetes (11% vs 16%, p = 0.033), anterior AMI (41% vs 55%, p <0.001), cardiogenic shock (9% vs 14%, p = 0.029), anterograde TIMI grade flow >1 (10% vs 21%, p <0.001), and a greater incidence of preinfarction angina (43% vs 32%, p = 0.001), multivessel disease (59% vs 47%, p = 0.001), and total chronic occlusion (20% vs 10%, p <0.001). At 6 months, the mortality rate was lower in patients with CC compared with patients without CC (4% vs 9%, p = 0.011), whereas there were no differences in the incidence of reinfarction, target vessel revascularization, and angiographic restenosis. After multivariate analysis, CC did not emerge as a significant variable in relation to 6-month clinical and angiographic outcomes. CC does not exert a protective effect in patients who undergo mechanical intervention in the first 6 hours of AMI onset.