OBJECTIVE: To understand family member consent decision-making influences and experiences in Malawi in order to inform future minimally invasive tissue sampling (MITS) studies. DESIGN: Qualitative study. SETTING: Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, which serves as the central referral hospital for southern Malawi and where MITS participants were recruited from. PARTICIPANTS: Families of paediatric MITS participants. METHODS: We conducted in-depth interviews with 16 families 6 weeks after the death of paediatric MITS participants. Data were analysed using a combination of thematic content and theoretical framework approaches to explain the findings. RESULTS: Improved cause of death (CoD) ascertainment was the principal motivator for participation to protect remaining or future children. Community burial norms, religious doctrine and relationships with healthcare workers (HCWs) were not reported influencers among family members who consented to the procedure. Primary consenters varied, with single mothers more likely to consent independently or with only female family members present. Clear understanding of MITS procedures appeared limited 6 weeks postprocedure, but research was described as voluntary and preconsent information satisfactory for decision-making. Most families intended to share about MITS only with those involved in the consent process, for fear of rumours or judgement by extended family members and the wider community. CONCLUSION: Among those who consented to MITS, decision-making was informed by individual and household experiences and beliefs, but not by religious affiliation or experiences with HCWs. While understanding of the MITS procedure was limited at the time of interview, families found informed consent information sufficient for decision-making. Future MITS studies should continue to explore information presentation best practices to facilitate informed consent during the immediate grieving period.