Abstract Background: Gastric cancer is the fourth most common cancer and highly prevalent in South Korea. Given its prolonged disease progression, understanding the impact of health expenditure patterns over time is crucial. This nested case-control study aimed to identify the association between health expenditure trajectory and incidence of gastric cancer. Methods: Data from the National Health Insurance Service Senior Cohort of South Korea were used. Individuals diagnosed with gastric cancer (N = 14,873) were matched to a non-diagnosed group (N = 44,619) in a 1:3 ratio using a nested case-control design. A latent class trajectory analysis was performed to identify the patterns of health expenditure among the matched participants. Furthermore, conditional logistic regression analysis was conducted to examine the relationship between healthcare expenditure trajectories and gastric cancer incidence. Results: Seven distinct health expenditure trajectories over a 5-year period were identified: consistently lowest (13.9%), rapidly increasing (6.4%), gradually increasing (14.1%), consistently second-highest (22.1%), middle-low (17.8%), gradually decreasing (12.8%), and consistently highest (12.9%). Compared to the Middle-low group, individuals in the rapidly increasing (OR = 2.07; 95% confidence interval [CI], 1.90–2.25), consistently lowest (OR = 1.43; 95% CI, 1.33–1.55), gradually increasing (OR = 1.23; 95% CI, 1.15–1.32), and consistently highest (OR = 1.08; 95% CI, 1.01–1.17) groups exhibited a higher risk of developing gastric cancer. Conclusion: Our findings emphasize the importance of monitoring health expenditures to prevent gastric cancer. The categorization of health expenditure by trajectories allowed the identification of specific risk groups that may be targeted by appropriate interventions. Citation Format: Minjee Lee, Ki-Bong Yoo, Woo-Ri Lee. Health expenditure trajectory and gastric cancer incidence in the National Health Insurance Senior Cohort: A nested case-control study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A001.