Compartment syndrome resulting from pitviper envenomation is uncommon in North America; however, when it does occur, early diagnosis, optimal antivenom therapy, and possible surgical decompression are the primary means of preventing the complication of neuropathy. Here, we report a case of a rattlesnake envenomation in the anterior compartment of the lower leg that required high doses of morphine to control pain. Although compartment syndrome was considered a possible outcome, subfascial pressures were not monitored and antivenom was discontinued at 24 hours. At 36 hours, the patient developed dorsal foot numbness and foot drop, and 15 hours later pressures within the anterior compartment were >68 mm Hg. Emergency fasciotomy was performed 59 hours postenvenomation. Peroneal neuropathy was evident after surgery and only partially recovered postoperatively. Earlier monitoring of subfascial pressures and using those pressures as a guide for decisions about time and dose of CroFab antivenom treatment may have permitted earlier surgical treatment after onset of compartment syndrome or even prevented the onset of this condition.