<h3>Objectives:</h3> To estimate the annual cost of wasted indocyanine green (ICG) used for sentinel lymph node (SLN) mapping in patients with localized endometrial cancer. <h3>Methods:</h3> We used the Surveillance, Epidemiology, and End Results (SEER) program database to estimate the number of annual cases of localized uterine cancer. We queried the Premier database (www.premierinc.com; Premier, Inc; Charlotte, NC) to determine the median cost to institutions and charge to patients associated with ICG. We searched Premier for all patients who underwent surgery for endometrial hyperplasia or uterine cancer from January 2006 to June 2018. Among 142,629 patients, there were 12,543,758 billing records. The median charge and median variable cost associated with ICG were estimated from 7,826 records that identified ICG use in the hospital charge description. To further validate these estimates, we conducted a separate search for lymph node sampling and radiopharmaceutical mapping to confirm these billings were separate from ICG billings. To perform the drug waste analysis, we assumed that gynecologic oncologists use 2-4 mL of the only currently available ICG vial kit (25 mg per 10 mL) per SLN case, resulting in presumptive waste of 60-80% of the total vial. Estimated waste was then calculated using the variable cost as a measure of institutional waste and charge as excess cost transferred to patients or payers. <h3>Results:</h3> In SEER 2020, there were 65,520 estimated cases of uterine cancer. Seventy percent of these cases (45,934) were localized and thus eligible for SLN mapping. The median cost associated with ICG was $56.70 (25%ile: $22.32; 75%ile: $71.00), and the charge was $419.34 (25%ile: $219.79; 75%ile: $527.47). The estimated annual waste associated with current ICG packaging was $1,562,674 - $2,083,566 to hospitals. The estimated annual excess charge imposed on patients or payers was $11,557,178 - $15,409,570. <h3>Conclusions:</h3> The annual cost of wasted ICG due to its current manufactured vial size is $1.5-$2.1 million for hospitals and $11.5-$15.4 million for patients. This is a gross underestimate, as it does not include cases of atypical hyperplasia or vulvar cancer, which would also be eligible for SLN biopsy. We suggest ICG vials should be packaged and sold in a 10-mg vial size to avoid drug waste and excess costs to institutions and patients.