Purpose Innovative small and medium-sized enterprises (SMEs) are key economic actors, but they are fragile. Their innovation trajectory requires an evolution in their competencies as their strategy evolves, and this is a particularly critical concern when they are engaged in both exploration and exploitation activities and want to develop organisational ambidexterity. In turn, this brings challenges for human resource management (HRM): some research studies have identified “mobilising” practices for innovation, but few authors have taken a dynamic approach. This study aims to fill this double-theoretical gap by answering the following two questions: how does HRM respond to the challenges associated with the search for ambidexterity in an innovative SME's trajectory? What HRM practices are mobilised in the innovation trajectory of SMEs? Design/methodology/approach The authors carried out two longitudinal case studies concerning innovative SMEs in the medical equipment sector, which are now over 10 years old and seeking to stabilise an ambidextrous way of operating. The authors conducted 37 semi-structured interviews in 2018–2019 and collected public and internal documents. For each case, the authors identified sequences (Bidart et al., 2013) displaying a certain homogeneity in terms of innovation strategy. The authors then performed a cross-case analysis. Findings These case studies produced two main results. First, the trajectory of innovative SMEs consisted of sequences during which competency needs and HRM practices evolved. Despite their similar modes of ambidexterity, the two SMEs have mobilised different human resource (HR) practices. Second, the HRM practices implemented struggle to support the firm at key turning points in the innovation trajectories and can even hinder such changes in direction. Originality/value The originality of this work lies in two major dimensions. First, the authors choose to explore innovation and the search for ambidexterity, two themes that are traditionally studied in large firms, in the setting of SMEs. Second, the authors choose a longitudinal method to explore the evolution over time in modes of ambidexterity and HRM, along these SMEs' innovation trajectory. This is a departure from more traditional approaches seeking to identify which HR practices, or configurations of practices, are best able to foster ambidexterity and innovation. It leads the authors to show, in a contingent, dynamic perspective, the importance of the Human Resources Foundation’s (HRF's) positioning and attitude in supporting diversified SMEs’ innovation trajectories. This requires allocation of the necessary resources to the function, which needs time and resources to reflect on how to build the ambidextrous HRM that is essential for the firm's survival.