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We examined trends in mortality from hepatitis C virus (HCV) infection and alcoholic liver disease (ALD) in the setting of drug overdose. Using US Census and national mortality records (2009‐2018), we identified deaths with HCV infection, ALD and drug overdose. HCV‐related mortality without drug overdose increased up to 2014, followed by a marked decrease. Mortality from HCV and drug overdose increased significantly. Whereas ALD‐related mortality without drug overdose continued to rise, no significant trend from ALD with drug overdose was noted. HCV‐related mortalities reduced after the introduction of DAA agents, while drug overdose‐related mortality in HCV was constantly increased. [ABSTRACT FROM AUTHOR]