BackgroundThere is a global interest in institutionalizing health technology assessment (HTA) as an approach for explicit healthcare priority-setting. Institutionalization of HTA refers to the process of conducting and utilizing HTA as a normative practice for guiding resource allocation decisions within the health system. In this study, we aimed to examine the factors that were influencing institutionalization of HTA in Kenya.MethodsWe conducted a qualitative case study using document reviews and in-depth interviews with 30 participants involved in the HTA institutionalization process in Kenya. We used a thematic approach to analyze the data.ResultsWe found that institutionalization of HTA in Kenya was being supported by factors such as establishment of organizational structures for HTA; availability of legal frameworks and policies on HTA; increasing availability of awareness creation and capacity-building initiatives for HTA; policymakers’ interests in universal health coverage and optimal allocation of resources; technocrats’ interests in evidence-based processes; presence of international collaboration for HTA; and lastly, involvement of bilateral agencies. On the other hand, institutionalization of HTA was being undermined by limited availability of skilled human resources, financial resources, and information resources for HTA; lack of HTA guidelines and decision-making frameworks; limited HTA awareness among subnational stakeholders; and industries’ interests in safeguarding their revenue.ConclusionsKenya’s Ministry of Health can facilitate institutionalization of HTA by adopting a systemic approach that involves: - (a) introducing long-term capacity-building initiatives to strengthen human and technical capacity for HTA; (b) earmarking national health budgets to ensure adequate financial resources for HTA; (c) introducing a cost database and promoting timely data collection to ensure availability of data for HTA; (d) developing context specific HTA guidelines and decision-making frameworks to facilitate HTA processes; (e) conducting deeper advocacy to strengthen HTA awareness among subnational stakeholders; and (f) managing stakeholders’ interests to minimize opposition to institutionalization of HTA.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12913-023-09673-4.