Introduction: We sought to compare antiemetic use after acetaminophen poisoning in patients treated with oral or intravenous (IV) N-acetylcysteine (NAC).Methods: Our retrospective chart review identified 20 orally treated patients and 17 IV-treated patients. For both groups, we calculated the total number of antiemetic doses given, their associated cost, and also determined parameters that correlated with antiemetic use.Results: IV-treated patients received fewer total antiemetic doses than those receiving oral NAC (1.1 Ϯ 0.2 vs. 2.8 Ϯ0.7; P ϭ0.04). Antiemetic cost correlated with doses received for both groups; however, because the regression lines differed (P ϭ0.02), antiemetic therapy cost was less in IV-treated patients. In addition, serum acetaminophen concentration correlated with total antiemetic doses in oral NAC patients (P Ͻ0.002) but not with IV treatment patients (P ϭ0.78).Conclusions: Intravenous NAC reduced antiemetic utilization, and it costs less than oral therapy. Furthermore, antiemetic use appeared to be determined by a combination of acetaminophen concentration and NAC administration route.