The efficacy and mechanism of a cold atmospheric-pressure air plasma (CAAP), which carries abundant atomic oxygen (OI), on blood coagulation are studied. The tests on sodium citrate mixed blood-droplet samples show that 1) The heat delivered by the CAAP has no impact on the observed clot formation, 2) Plasma effluent activates platelets to promote coagulation state and cascade, and 3) The degree of clotting increases with the OI flux delivered by the CAAP. The full clotting time is shortened from about 25 minutes of the natural clotting time to about 16 s of the CAAP treatment time. The tests on smeared blood samples show that the reduction of the platelet count and the increase of RBC count are proportional to the applied OI flux. In vivo tests, using swine as nimal model, swift hemostasis of large and deep cut wounds on the back by the CAAP treatment was demonstrated. A cut artery was sealed completely with 25 s treatment. The pressure applied by a finger on the cut artery could be removed immediately after the treatment and there was no re-bleed. Based on the in vitro test results and the animal model trials, CAAP coagulation mechanism is presented.