This study aims to explore families’ reflections on their decision to donate brain tissue to the NSW Tissue Resource Centre (NSW TRC), Australia. Specifically, the study aims to investigate respondents’ initial reactions to the request for donation, primary reasons for their decision, and subsequent satisfaction levels. Participants were next-of-kin (NOK) contacted between May 2002 and May 2008, on the day of their relative’s autopsy, who agreed to donate brain tissue to the NSW TRC for medical research. All 111 NOK were invited to participate, and those who agreed completed an anonymous questionnaire. Fifty completed questionnaires were received. Results showed that 74% of respondents were not upset by the donation call and 98% were satisfied with their decision to donate. Of the 22% who reported having been upset, many indicated that their distress was partly related to their circumstances. When asked the main reason for their donation, 66% had wanted to help others, or help research, while 24% stated their primary reason as a belief that they were respecting the wishes of their deceased relative. These findings show that NOK are not further distressed by being asked to donate brain tissue, give altruistic reasons for consent and are satisfied with the decision they made. In both this study and previous literature, the importance of discussion about organ donation amongst relatives is a recurring theme. Knowledge about a relative’s wishes is likely to help facilitate decision-making, overcoming at least one crucial barrier to lifting rates of organ donation for transplantation and research.