There is so far no international consensus concerning the prescription of antithrombotic agents in hemodialysis patients. It is not clear yet why they cause more bleeding in some patients and are beneficial in others. We therefore tried to find out what triggers bleeding in this population. This is an observational before-and-after study that included all patients undergoing hemodialysis in our center between 2005 and 2015. We divided the study into two phases: phase one (125 patients) where aspirin was used without restrictions and phase two (110 patients) where aspirin was avoided in severe hypertension and primary prevention. We aimed to assess the differential occurrence of intracerebral hemorrhage between the two phases and the cardiovascular mortality of patients whether on aspirin or not. Bleeding events occurred in 12.8% of patients in phase one and 13.6% in phase two (p = 0.85). Seven out of 125 patients (6%) in phase one experienced intracerebral hemorrhage and none in phase two. Intracerebral hemorrhage was significantly increased in those with the combination of aspirin and severe hypertension (p = 0.003). Aspirin and acenocoumadin were significantly associated with total bleeding (OR = 3.81 and 4.85 with p = 0.005 and 0.001 respectively). Cardiovascular mortality did not differ between phase one and two whether patients were on aspirin or not (p = 0.45 and 0.31 respectively). Minimizing aspirin use in hemodialysis patients with severe hypertension reduced intracerebral bleeding without a significant difference in cardiovascular mortality.