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Purpose The aim of this paper is to understand if service innovation (Helkkula et al., 2018), based on artificial intelligence (AI) systems, may guarantee healthcare service ecosystem (H-SES) well-being (Frow et al., 2019; Beirão et al., 2017), taking into account that many doubts relieved in terms of transparency may compromise the patients' perceived quality of health services provided through AI systems. Design/methodology/approach A literature review on service innovation, detected in terms of value co-creation, and service ecosystem, investigated in terms of well-being, is drawn. To analyze the implications of service innovation on a H-SES well-being, through the technology acceptance degree and predisposition to use by actors, a case study based on TAM-model 3 determinants as categories is carried out. Findings AI-based service innovation archetypes in healthcare may be considered as antecedents of the service ecosystem well-being conditions as long as they enable actors to co-create value. To make it possible, a patient-driven service innovation is necessary in order to mitigate the risks of its inactivity due to fears in terms of transparency. Originality/value Service innovation and service ecosystem well-being may be studied in an integrated way, with a multidisciplinary approach, and are linked by value co-creation, because only thanks a patient-driven service innovation is possible to foster service ecosystem well-being in healthcare.