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Abstract Aim Pandemics of life‐threatening viruses have detrimental impacts on the motivation of healthcare workers to work. However, no study has examined this impact during different pandemics with the same setting and design. This study aimed to reveal similarities and differences in factors associated with willingness and hesitation to work between two recent pandemics, H1N1 influenza and COVID‐19, in the same hospital, using the same questionnaire. Methods Healthcare workers in one hospital in Japan completed a questionnaire on basic characteristics and stress‐related questions during the H1N1 influenza (n = 1061) and the COVID‐19 (n = 1111) pandemics. Logistic regressions were performed to ascertain the effect of personal characteristics and stress‐related questions on the likelihood that employees showed strong or weak motivation or hesitation to work. Results The feeling of being protected by the hospital was the only factor that significantly decreased hesitation and increased motivation to work, and females felt significantly more hesitation to work than males did in both pandemics. Conclusions Hospital managers and government officers should focus on increasing organizational support and caring for female workers to maintain healthcare workers' motivation to work during future pandemics.