OBJECTIVES: Trastuzumab has been shown to be an effective add-on treatment to chemotherapy as a first-line therapy for patients with metastatic gastric cancer with an overexpression of human epidermal growth factor receptor 2 (HER2). This study looks to test the cost-effectiveness of trastuzumab for adult patients from a United States societal perspective. METHODS: Data from the Trastuzumab for Gastric Cancer clinical trial (ClinicalTrials.org Identifier Number: NCT01041404) was used in a three health-state Markov cohort model. Costs were then calculated from the United States societal perspective. Drug, caregiver, administrative, palliative care, and adverse event costs were found through the literature as well as through current fee schedules from CMS and the US Department of Veteran Affairs. Costs and outcomes were discounted at a rate of 3%. All costs were converted to a November 2015, US dollar base year using the Medical CPI from the Bureau of Labor Statistics. RESULTS:   Trastuzumab in combination with chemotherapy (combination of either capecitabine and cisplatin or flouroracil and cisplatin) as a first-line therapy to treat metastatic gastric cancer was found to have an incremental cost-effectiveness ratio of $150,452 per QALY gained when compared to chemotherapy alone. The one-way sensitivity analysis at +/- 20% for all parameters found that the most sensitive parameters were median overall survival and median progression free survival of both the trastuzumab + chemotherapy and chemotherapy alone treatments, as well as utility of progression free survival and progressed disease. Overall, the model is robust as it is not sensitive to any of the other parameters. CONCLUSIONS: Trastuzumab in combination with chemotherapy as a first-line treatment is likely to be cost-effective for adult metastatic gastric cancer patients with an overexpression of HER2 with a cost per QALY gained just above the $150,000 U.S. willingness to pay threshold recommended by the World Health Organization.