The hepatitis C virus is responsible for more deaths in the United States than any other infectious disease, and hepatitis C infections have been rising at an alarming rate since 2010. We evaluated the role of the opioid epidemic and, in particular, the 2010 introduction of an abuse-deterrent version of OxyContin. The OxyContin reformulation led some users of the drug to switch to heroin, which could have exposed them to the hepatitis C virus. We used difference-in-differences methods, using data for the period 2004–15, to assess whether states with higher rates of OxyContin misuse prior to reformulation—states where the reformulation had more impact—experienced faster growth in infections after the reformulation. States with above-median OxyContin misuse before the reformulation experienced a 222 percent increase in hepatitis C infection rates in the post-reformulation period, while states with below-median misuse experienced only a 75 percent increase. These results suggest that interventions to deter opioid misuse can have unintended long-term public health consequences.