Intravenous infusion of a subanesthetic dose of ketamine has been shown to improve neuropathic pain. However, ketamine-induced liver injury can occur. Reported here are 2 cases with substantial liver enzyme elevations less than 2 days after initiation of repeat ketamine infusion at least 7 months after the last infusion. Although their liver enzymes normalized within a few weeks, it is unclear what the long-term consequences are. Furthermore, drug-induced liver injury can cause acute liver failure. Therefore, we recommend close monitoring of liver enzymes every 1 to 2 days during ketamine infusions.