Aims: Radial access was associated with a significant reduction in major bleeding, compared to femoral access, in the treatment of ST segment Elevation Myocardial Infarction (STEMI). It is not yet clear its impact on in-hospital mortality. The aims of this study are to compare in-hospital mortality in patients undergoing primary PCI via radial access or femoral access, based on the Portuguese Interventional Cardiology Registry (PICR), and evaluate the interaction with the use of glycoprotein IIbIIIa (GP IIbIIIa) inhibitors. Methods and results: 6559 consecutive pts with STEMI undergoing primary PCI prospectively included in the PICR from Jan/2007 to Dec/2012. Radial access was used in 1384 pts (21%) and femoral access in 5175 (81.9%). We compared demographic and clinical variables between the 2 groups. Independent predictors of in-hospital mortality were identified by multivariate analysis. The interaction with the use of GP IIbIIIa inhibitors was also evaluated. In-hospital mortality occurred in 3.3% of pts undergoing primary PCI via femoral access and in 0.8% of pts undergoing primary PCI via radial access (p <0.01). After multivariate analysis, radial access was an independent predictor of in-hospital mortality (OR 0,3; IC 0,125-0,699, p=0,006). Other predictors identified in the model were age ≥65 years (OR 3.1, IC 1.940-4.816, p<0.001), history of heart failure (OR 3.0, IC 1.144-7.910, p=0.026), history of peripheral artery disease (OR 8.5, IC 4.693-15.472, p<0.001), history of smoking (OR 0.5, IC 0.332-0.862, p=0.010), hemodynamic support (OR 8.9, IC 5.622-14.194, p<0.001), left main PCI (OR 4.7, IC 2.246-9.834, p<0.001), right coronary artery PCI (OR 1.7, IC 1.182-2.559, p=0.005). The benefit of choosing radial access over femoral access was independent from Gp IIbIIIa inhibitors use (p for interaction NS). Conclusion: In this population of STEMI pts undergoing primary PCI, radial access was associated to a lower in-hospital mortality regardless the use of Gp IIbIIIa inhibitors.