OBJECTIVE: Etoposide is an antineoplastic agent widely used to treat pediatric and adult cancers. Critically ill patients are expected to receive several intravenous pharmaceutical drugs while admitted to hospitals. When compatibility data are available, intravenous drugs may be administered simultaneously through the Y-site. This study aimed to determine the compatibility of etoposide during simulated Y-site administration with 45 continuous-infusion drugs that are commonly administered in tumor critical care units. METHODS: Etoposide was diluted to a concentration of 0.25 mg/mL in 0.9% sodium chloride (NS) and other intravenously tested drugs were reconstituted according to the manufacturer's recommendations to the final clinical desired concentrations. Y-site administration was simulated in vitro by mixing 5 mL etoposide with other diluted intravenous medications under aseptic conditions in a 1:1 ratio. Compatible solutions were withdrawn at certain time intervals (0, 1, 2, 4 hours) after mixing and tested visually, using a Tyndall beam, pH, turbidity, insoluble particles, and UV absorption as measures of compatibility. RESULTS: Etoposide was compatible with 38 (84%) of the 45 drugs tested within four hours. Glutathione and human granulocyte colony-stimulating factor immediately showed incompatibility with etoposide. Within 1 h, four medications (cefuroxime sodium, ilaprazole sodium, mycophenolate, and xuebijing) were incompatible. Within 4 h, one medications (ceftazidime) were also found to be incompatible with etoposide under observation. CONCLUSION: Seven of the 45 common medications in tumor critical care tested with etoposide were incompatible within 4 h. If co administration is inevitable and the drug is infused through a port catheter, a larger volume of saline (NS) or dextrose 5% in water (D5W) should be used to flush the port catheter before and after the etoposide infusion to clean the lumen of the port catheter.