Background: Based on the results from the TOPAZ-1 study, current standard of care treatment for patients with advanced biliary tract cancer is gemcitabine and cisplatin (Gem/Cis) plus durvalumab (Durva). The addition of Durva improved progression-free survival (PFS) and overall survival (OS) compared to Gem/Cis alone. Considering that the epidemiology of cholangiocarcinoma may indicate some racial and ethnic groups may have a higher incidence and poorer prognosis; we present a cost analysis of this new treatment option. Methods: We calculated the unit prices of Durva and Gem/Cis with the information provided by the LexiComp (accessed September 2022). The drug cost per cycle was calculated for each drug; assuming an average patient surface area of 1.9m² for men and 1.6m² for women. In both cases, the chosen vial was the same and, thus, pricing was the same. Costs of administration, adverse effect and follow up were excluded. As per the TOPAZ-1 study design, the first 8 cycles included either Durva (day 1) + Gem/Cis (days 1 and 8) or placebo (day 1) + Gem/Cis (days 1 and 8) every 3 weeks, followed by Durva or placebo alone every 4 weeks until disease progression. The total treatment cost was composed of the sum of all treatment cycles received on study. Cost per life year gained was calculated using the total cost per year in each group and treatment duration as the denominator. Results: Cost per cycle for Durva, Gem, and Cis was $13,797, $282, and $87, respectively. The patients in the TOPAZ-1 trial who were randomized to the Durva arm had a median treatment duration of 7.3 months while patients in the Gem/Cis arm had a median treatment duration of 5.8 months. PFS was similar with a median time of 7.2 months and 5.7 months, respectively. This difference in both treatment duration and PFS (both 1.5 months) was associated with an increased cost of $124,170 over the course of treatment for Durva + Gem/ Cis compared to Gem/Cis alone ($127,119 vs $2,949). Durva + Gem/Cis has a medication only cost of $1,655,604 per life year gained as compared to Gem/Cis alone. Total yearly cost by treatment arm was higher for the Durva + Gem/Cis group ($209,899 vs $2,949). Conclusions: Durvalumab combined with gemcitabine and cisplatin is associated with an increase of 1.5 months in both treatment duration and PFS without additional toxicity observed when compared to Gem/Cis alone; however, Durva + Gem/Cis was associated with a drug cost over 40 times higher when compared Gem/ Cis alone for first-line treatment of advanced biliary tract cancer. Further research should focus on cost-effective solutions to treat advanced cholangiocarcinoma.