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Objective: We have compared the impact of access strategy change on early and two-year outcomes after primary percutaneous coronary intervention using trans-radial access (TRA) versus intervention by trans-femoral access (TFA). Background: Adoption of TRA was recently proposed as potentially beneficial strategy to improve outcomes of PPCI for STEMI patients. Methods: We have studied 1808 consecutive patients which underwent TFA (n=646) and TRA (n= 1162) intervention for STEMI at our institution between 2007 and 2010. This was all-comers study regardless patient acute clinical presentation of STEMI. We have compared the cardiac mortality and the MACE rates (composite of death, stroke, re MI and TVR) after two years of follow up. Results: The majority of deaths occurred as early events in the first 30 days from STEMI. The major difference in early mortality rates was in favor of TRA strategy (5.2% or 60deths) comparing TFA strategy (10.5% or 68 deaths) (OR 0.46; 95% CI [0.32-0.66], p< 0.001). TRA was also associated with significant 30 days MACE rate reduction (7.3% vs. 12.5%, HR 0.55; 95% CI [0.39-0.76], p< 0.001). Following the first year of follow up additional 1.7% and 1.0% of deaths occurred in both groups respectively. At two years follow up there were 93 deaths (8.0%) mortality rate in TRA group comparing to 90 deaths (13.9%) in TFA group (OR 0.60; 95% CI [0.47-0.89], p=0.001). The difference obtained in the first 30 days between the two accesses strategies have sustained with similar trends for mortality rates in the following two years. Two year MACE rates were in favor of TRA strategy (14.6% Vs 22.1%; OR 0.56; 95% CI [0.43-0.78], p< 0.001). Cumulative survival curves were created to illustrate findings. Conclusions: Our study confirmed that transradial access strategy for primary coronary intervention is associated with significant early and two years MACE rate reduction comparing to default transfemoral access strategy for primary coronary interventions in STEMI patients. TRA was associated with sustained mortality benefit after two years.