This study was aimed at researching the reasons why mothers enrol their children in malaria clinical research and how family members or relatives are involved in the decision-making process. Issues related to informed consent were also a particular focus of this study. A total of 81 participants took part in 8 focus group discussions. Thirty-nine participants were recruited from Blantyre, an urban setting, and forty-two participants were from Chikwawa, a rural setting. All the participants were mothers whose children had participated or were participating in the Intermittent Prevention Therapy post-discharge (IPTpd) Malaria Research. A majority of the participants reported that they chose to participate in the IPTpd research as a way of accessing better quality medical care. They also decided to enrol their children in order to benefit from the material and monetary incentives that were being given to participants for their participation. Most participants reported that they made the enrollment decisions on their own. They informed their family members/marital partners about their enrollment decisions after they had given their consent. A few made their enrollment decisions after consulting their family members. There was also a sense of trust in health workers who asked the potential participants to join the IPTpd research. Most participants decide to take part in malaria research because of better medical treatment. Partners and relatives play a very small role in the decision-making process of participants in malaria clinical research. Research participants'have a sense of trust in health workers who enrol them in clinical research.