PURPOSE: Nivolumab dosage was initially selected on the basis of body weight, often resulting in leftover drug after sterile compounding. This study sought to investigate the real-world wastage of nivolumab and assess the long-term stability of leftover nivolumab within vials to facilitate drug vial optimization (DVO). METHODS: We collected all discarded vials after preparation from 17 regional hospitals in Japan over a 6-month period preceding the adoption of a fixed dose of 240 mg per administration. The actual amount of waste was measured for each preparation. Stability assessment was performed under different storage conditions. RESULTS: A total of 2,789 100-mg vials and 4,069 20-mg vials were collected. Overall, the drug cost associated with the expenditure of nivolumab alone was $12.1 million, whereas the total cost due to drug wastage was $0.735 million (rate of wastage, 6.1%). Furthermore, the immunoglobulin G concentrations of nivolumab remaining within vials, as well as binding activity to programmed death-1 protein, did not change significantly over 4 weeks of storage at either 4°C or room temperature. CONCLUSION: Significant drug wastage occurs during sterile preparation of nivolumab according to body weight–based dosing. Although nivolumab dosing has been changed to a fixed dose in Japan, body weight–based dosing is still applied in some other countries, as well as in combination therapy with ipilimumab. Our findings regarding the long-term stability of leftover nivolumab within the vials should motivate hospitals to implement DVO for cost savings.