For a study, researchers sought to investigate the Interagency Registry for Mechanically Assisted Circulatory Support registry to test the hypothesis that such a history would be associated with poorer outcomes. Patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support registry. They received a continuous-flow left ventricular assist device (LVAD) between June 2006 and December 2017 and were considered eligible for inclusion in the study. The median period of follow-up was 12.9 months (interquartile range, 5.3 to 17.5). The final study group comprised 15,069 patients, of whom 1,184 (7.9%) had a history of alcohol addiction, and 1,139 (7.6%) had a history of illegal substance use. The total mortality rates for the alcohol group, the illegal drug group, and the control group were 25%, 21%, and 29%, respectively. Cox regression analysis revealed that a history of alcohol abuse (hazard ratio, 0.97, 95% CI, 0.84 to 1.13, P=0.72) or illicit drug use (hazard ratio, 1.02, 95% CI, 0.86 to 1.21, P=0.81) was not significantly associated with an increased risk of all-cause mortality in the LVAD population as a whole. In contrast, after controlling for other factors, a history of alcohol consumption or illicit drug use was substantially associated with higher device malfunction/pump thrombosis, device-related infection, or hospitalization for all causes (all P<0.05). In addition, as compared to patients who did not receive the device, those who had their LVADs implanted experienced a lower quality of life than those who did. This was determined by using the Kansas City Cardiomyopathy Questionnaire. In conclusion, the data suggested that patients with a history of heavy drinking or illicit drug use were at a higher risk for negative device-related events and an even worse quality of life following the installation of continuous-flow LVADs than the overall LVAD population. This was the conclusion reached after comparing the patients with a history of alcohol misuse or illicit drug use to the overall LVAD population.