Due to the need for concurrent use of N-acetylcysteine (NAC) and ondansetron in the event of acetaminophen overdose, a Y-site intravenous (IV) apparatus for these drugs would be practical. It is known that nausea and vomiting are common side effects of both acetaminophen overdose and NAC administration. Current standard patient care using NAC involves interruption of IV NAC infusion to give an IV bolus dose of ondansetron, which creates an unnecessary opportunity for healthcare staff errors and patient complications. To evaluate the IV compatibility of NAC and ondansetron, medical grade tubing was connected via a closed-circuit IV pump with separate channels. Doses of NAC were circulated in individual channels based on weight-based dosing protocols (30-kg and 100-kg patient does). Ondansetron (4 mg) was introduced into the flow of NAC using the Y-site. Samples of the circulated solutions were gathered in triplicate at time points of 10, 20, and 30 minutes after combination of ondansetron and NAC. Concentrations of NAC were quantified using a validated high performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Once the collected samples underwent HPLC-UV analysis, data was produced that showed promise for compatibility between ondansetron and NAC with Y-site infusions. Comparison of NAC concentrations for the channels with and without ondansetron yielded no statistically significant difference between the treatments (p-value of 0.05). From this experiment, we concluded that introduction of ondansetron into the flow of NAC IV would not impact NAC concentration. As mentioned before, this study was conducted using only two doses in vitro, which may be a point for further exploration of a varied number of N-acetylcysteine doses.