Background The aim of this study was to analyze the effect of device-dependent factors on epistaxis episodes comparing patients supported with a continuous-flow left ventricular assist device (CF-LVAD) to patients under the same antithrombotic therapy. Methods Patients who underwent CF-LVAD between 2012 and 2018 were reviewed retrospectively from the institutionally adopted electronic database. Patients who underwent mitral valve replacement (MVR) surgery receiving the same anticoagulant and antiaggregant therapy were included as a control group. Demographics, epistaxis episodes, and nonepistaxis bleeding between the two groups were compared. Results A total of 179 patients met the inclusion criteria (61 patients CF-LVAD group, 118 patients MVR group). The median (range) follow-up periods for the study (CF-LVAD) and control (MVR) groups were 370 (2819) and 545.70 (2356) days, respectively. There was a significant difference for frequency of bleeding episodes per month between CF-LVAD and MVR groups (p = 0.003 < 0.05). The most common site of bleeding was the anterior septum in both groups (90.9% for the CF-MVR group and 100% for the MVR group). While 14 patients (23%) had nonepistaxis bleeding in the CF-LVAD group, only two patients (1.7%) had nonepistaxis bleeding in the MVR group. There were significant differences in nonepistaxis bleeding rates between the CF-LVAD and MVR groups (chi(2)=19.79,p < 0.001). Conclusion Both epistaxis and nonepistaxis bleeding rates were higher in the CF-LVAD group than in the MVR group. This suggests that the use of CF-LVAD support could directly increase the risk of hemorrhagic complications.