This study evaluated whether radial access intervention had a lower risk of post-treatment adverse events in acute coronary syndrome (ACS) even in Japan where the use of a strong antithrombotic regimen was not approved. We retrospectively analyzed a large nation-wide registry in Japan to compare the incidence of post-treatment adverse events according to the types of vessel access (trans-radial; TRI vs. trans-femoral; TFI) among ACS cases (n = 76,835; 43,288 TRI group and 33,547 TFI group). Primary outcome was a composite of in-hospital death, myocardial infarction associated with percutaneous coronary intervention, bleeding complication requiring transfusion, and stent thrombosis during in-hospital stay. Propensity score matching (PS) and instrumental variable (IV) analyses were used to account for treatment selection. The incidence of post-treatment adverse events was lower in the TRI group by 0.95% compared to the TFI group with PS (p < 0.001) and by 0.34% with IV (p = 0.127). A significantly lower risk for access site bleeding was observed by 0.34% with PS (p < 0.001) and by 0.53% with IV (p < 0.001). Radial access was related to a significantly lower risk for access site bleeding compared with femoral access, even without strong antithrombotic drugs for ACS in Japan, and may also relate to lower risk for a wider set of post-treatment adverse events.