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To compare US trends in rates of injection drug use (IDU), specifically opioid injection, with national trends in the incidence of acute HCV infection to assess whether these events correlated over time.We calculated the annual incidence rate and demographic and risk characteristics of reported cases of acute HCV infection using surveillance data from 2004 to 2014 and the annual percentage of admissions to substance use disorder treatment facilities reporting IDU for the same time period by type of drug injected and demographic characteristics. We then tested for trends.The annual incidence rate of acute HCV infection increased more than 2-fold (from 0.3 to 0.7 cases/100 000) from 2004 to 2014, with significant increases among select demographic subgroups. Admissions for substance use disorder attributed to injection of heroin and prescription opioid analgesics increased significantly, with an almost 4-fold increase in prescription opioid analgesic injection. Significant increases in opioid injection mirrored those for reported cases of acute HCV infection among demographic subgroups.These findings strongly suggest that the national increase in acute HCV infection is related to the country’s opioid epidemic and associated increases in IDU.