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The post-entry operation sustainability of airline routes directly affects their profitability. This paper investigates factors influencing the operating duration of airline routes based on a survival analysis modeling method. Key factors are selected from five aspects representing characteristics in terms of cost and supply, route and airport, market structure, airline cooperation type, and time heterogeneity. The transatlantic market between Europe and the US is chosen as the empirical study due to its high degree of liberalization. The research period ranges 19 years from 2003 to 2021. First, the single factor analysis is conducted by utilizing the Kaplan-Meier method. Second, a Weibull parameter survival model is constructed to quantitatively analyze the relationship between the chosen factors and the operating duration of airline routes. The results show that：(1) The average operating duration of the EU-US routes is five years, among which routes that were continuously operated for more than 10 years account for 16%；(2) the operating duration of airline routes is significantly influenced by distance, airline’s total capacity, route structure, endpoint airports type, route competition, airline type, and region as well as alliance；(3) both independent and interaction variables representing alliance and code-share characteristics have significant impacts on route operating duration. Routes operated by Star and SkyTeam members have a longer operating duration. For airlines in the same alliance, the route-exit risks between operating carriers and marketing carriers in code-sharing cooperation are significantly different. [ABSTRACT FROM AUTHOR]