Background: Oldest-old persons frequently receive potentially inappropriate medication. Medication use takes place under the patients' informal caregivers' influence. We explored informal caregivers' perspectives on medication of (relatively) independent oldest-old persons to identify starting points for safer medication prescription/handling.; Methods: In this exploratory qualitative interview study we interviewed 45 informal caregivers of 45 oldest-old persons (23 with potentially inappropriate medication/22 without potentially inappropriate medication). Interviews were recorded, transcribed and content analyzed (deductive/inductive coding).; Results: Interviewees had little knowledge about/influence on oldest-old persons' medication, but declared to monitor oldest-old persons' needs for assistance. They were unaware of the concept of potentially inappropriate medication but sometimes sensitive to substance dependency. Most informal caregivers were satisfied with the oldest-old persons' medication and viewed medication as increasing the patients' quality of life. Inadequate communication was found between informal caregivers and general practitioners.; Conclusions: Influence of informal caregivers on (relatively) independent oldest-old persons' medication seems low. Stakeholders need to be aware that there is a transitional period where independency of oldest-old persons decreases and support needs increase which may be missed by (in-)formal caregivers or concealed by oldest-old persons. Monitoring patients' medication competencies; measures supporting communication between informal caregivers and health care professionals; provision of educational and support resources for informal caregivers and the acceptance of oldest-old persons' increasing assistance needs may increase medication safety.