Vaccine hesitancy remains a critical public health challenge in Nigeria, underpinned by entrenched medical mistrust that extends beyond individual decision-making to encompass systemic and sociological factors. This study examines the sociological determinants of medical mistrust and vaccine hesitancy among residents of Kwara State, structured around four objectives: to explore perceptions of medical institutions, determine the prevalence of hesitancy, assess the influence of social media on healthcare trust and analyse patterns of mistrust across demographic groups. The study is theoretically anchored in Structural Functionalism, which conceptualises healthcare institutions as vital to social stability yet susceptible to dysfunction when failing in competence, fairness and responsiveness. A mixed-methods approach was adopted, comprising a cross-sectional survey of 620 adults drawn from urban, peri-urban and semi-rural communities, complemented by semi-structured interviews with 30 participants. The findings reveal pervasive institutional mistrust: fewer than 35% of respondents perceived government health facilities as competent (31.9%), transparent (23.2%) or responsive (22.6%), while disagreement exceeding 40–49% was reported across indicators of institutional performance, accessibility, affordability and respectful treatment. Vaccine hesitancy affected 47.6% of participants, with the highest prevalence among women (49.9%), young adults aged 18–29 (57.3%), individuals with secondary education or below (55.9%), minority ethnic groups (53.7%) and those of low socio-economic status (57.9%).

Logistic regression analysis confirmed elevated odds of mistrust among women (OR 1.36), young adults aged 18–29 (OR 1.83), lower-educated respondents (OR 1.75), minority ethnic groups (OR 1.51) and low-SES individuals (OR 1.84). Engagement with social media emerged as a significant factor, with participants who trusted online vaccine information reporting 53.1% hesitancy, particularly on platforms such as Twitter and those participating in vaccine-related discussions exhibiting higher hesitancy levels. Qualitative insights highlighted structural neglect, disrespectful treatment, social marginalisation and the pervasiveness of digital misinformation as reinforcing both institutional mistrust and vaccine reluctance. The study concludes that vaccine hesitancy represents a behavioural expression of broader societal dysfunctions, institutional inadequacies and social inequalities rather than a simple deficit in knowledge. It recommends enhancing transparency and accountability within healthcare institutions, developing targeted interventions for marginalised populations, countering misinformation on social media and strengthening community health literacy to rebuild trust and improve vaccine uptake.