Randomized controlled trials (RCTs) have yielded conflicting results about the impact of transradial access (TRA) versus transfemoral access (TFA) in patients with ST-segment elevation myocardial infarction (STEMI). We performed a trial sequential analysis (TSA) of RCTs comparing TRA and TFA in patients with STEMI. The outcomes of interest were 30-day mortality, major bleeding, major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and access site complications. A total of 17 studies with 11,992 patients were included in the current TSA. The TRA group had lower 30-day mortality (risk ratio [RR] 0.72, 95% CI 0.58-0.90, P = .003), major bleeding (RR 0.62, 95% CI 0.49-0.79, P = .0001), MACE (RR 0.74, 95% CI 0.58-0.93, P = .01), and access site complications (RR 0.37, 95% CI 0.28-0.48, P < .00001). There was no difference in MI and stroke between the 2groups. Applying TSA boundaries, the z-curve for 30-day mortality, major bleeding, MACE and access site complications crossed the conventional and the TSA boundaries, indicating firm evidence for better outcomes in the TRA group. For MI and stroke, the z-curve failed to cross the conventional and the TSA boundaries for both outcomes, indicating lack of signals of benefit or harm. In the current TSA, the available data from RCTs support improved 30-day mortality, major bleeding, MACE and access site complication rates in STEMI patients treated by PCI through the radial access.