Residual dried blood spots from millions of newborns are being stored and used for research. The state of Michigan proactively developed a broad consent process for research use of newborns' blood spots. However, the extent to which mothers make informed choices about this research is unclear. A descriptive, qualitative study was conducted examining this issue. Twenty-nine observations of the consent process and 20 semistructured interviews were conducted with mothers on the postpartum unit of a large, academic hospital in Michigan. Content analysis of the transcripts was conducted. While most mothers agreed to donate the blood spots (n = 14/20; 70%), findings indicated that most decisions were uninformed (n = 16/20; 80%), as mothers lacked knowledge of biobanking research. Misunderstandings about anonymity, the consenter's credentials, and entity conducting the research seemed to influence decision making. Suggestions for improving the consent process include (1) changing the venue of blood spot education and consent from the postpartum period to the perinatal period, (2) strengthening the depth of information and delivery of information provided about the topic, including ethical and values clarification, and (3) increasing consenter education and training. Implementation may help increase the proportion of informed decisions.