Remdesivir is a direct‐acting nucleoside RNA polymerase inhibitor with activity against the novel SARS‐CoV‐2 virus used in the treatment of COVID‐19 pneumonia . Here we present two cases of suspected remdesivir‐associated acute liver failure (ALF) in which the liver failure improved following continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there is very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non‐acetaminophen‐induced ALF is limited. It is important to consider the risk of remdesivir‐associated ALF when weighing the risk vs. benefits of use, and acetylcysteine may have a role in its management.