ObjectiveIn recent years, full childhood routine immunisation coverage has fallen by 5% to levels not seen since 2008; between 2019 and 2021, 67 million children were undervaccinated. We aimed to identify and describe the determinants of vaccination drop-out from the perspectives of caregivers and health workers in Malawi.DesignWe used a community-based participatory research approach to collect data through photo elicitation, short message service exchanges, in-depth interviews and observations. We used a team-based approach for thematic analysis, guided by the Behavioural and Social Drivers of Vaccination framework.SettingThe study was conducted in Lilongwe and Mzimba North Districts in Malawi, representing urban and rural settings, respectively.ParticipantsParticipants included caregivers of partially vaccinated (n=38) and fully vaccinated (n=12) children between 25 and 34 months and Community Health Workers (n=20) who deliver vaccines. Caregiver participants were identified through health facility vaccination registers and with the assistance of community health volunteers.ResultsWe identified five principal drivers of routine vaccination drop-out: (1) poor caregiver knowledge of the vaccine schedule and how many vaccines are needed for full vaccination; (2) caregivers’ fear of repercussions after not following vaccination guidelines; (3) rumours and concerns if vaccines are repeated or new ones are introduced; (4) high opportunity cost of health facility visits, exacerbated by wait times, stockouts and missed opportunities and (5) limited family support and vaccination burden placed largely on mothers. Key differences between rural and urban settings related to practices around health cards and vaccine wastage, wait times, migrant and tenant communities, and social support systems.ConclusionsImmunisation interventions should be tailored to address drivers of drop-out in the community, the health facility and beyond. Service quality, timeliness and reliability need to be improved, and tailored messaging and education are needed, especially in response to COVID-19-related misinformation and introductions of new, routine vaccines.