Little is known about the health-related quality of life (HRQOL) following adverse bleeding events associated with antithrombotic drug therapy. This systematic review assesses the HRQOL of patients who suffered a bleeding event related to antithrombotic drug use. A literature search was performed using PubMed, EMBASE, and the Cochrane Library from inception through June 16, 2017. Studies measuring HRQOL after a bleeding event related to antithrombotic drug therapy for primary or secondary prevention of a thromboembolic event were included. Four studies with a total of 13,209 patients met the inclusion criteria, and of them, 3,649 patients developed a bleeding event. Patients who were included received antithrombotic drugs because of acute myocardial infarction or atrial fibrillation. EQ-5D, SF-36, and GHP MOS-13 were used to measure HRQOL. The follow-up time ranged from 6 to 29 months. Patients who suffered a bleeding event reported worse HRQOL compared to those who did not (EQ-5D – average increase on all domains of 0.09, p-values ranging from