The influences of aspirin and of acetaminophen on hemostasis were studied in normal healthy volunteers and in patients with either severe hemophilia A or hemophilia B. Acetaminophen did not alter the template bleeding time or the results of tests of platelet function in either group. Aspirin did prolong the template bleeding time and impaired platelet aggregation; these changes were most pronounced in patients with either form of hemophilia, and some (7/19) required plasma component therapy. Neither drug influenced the coagulation proteins or the fibrinolytic mechanism, as measured. The influences of a single dose (ranging from 975 to 1,950 mg) of acetaminophen and of a single dose (ranging from 325 to 2,925 mg) of aspirin were similar to those observed in persons receiving multiple doses. Acetaminophen is preferred in patients in whom a hemostatic influence is undesirable. However, either aspirin or acetaminophen can be used in normal healthy subjects.