The healthcare environment is becoming increasingly dependent on health information technology (HIT), with healthcare providers, patients, and other people engaged in the field producing and sharing information to improve healthcare delivery. This focus has raised the issue of Health Information Infrastructure (HII) to the forefront of policy, design, and law. While several studies have examined each element of HII, little attention has been paid to the overall infrastructure as a collection of technologies, institutions, standards, and practices. In order to fill the gap, this study focuses on medication reconciliation as an example of the wider phenomenon of HII. In particular, the study examines a medication reconciliation process (MRP) as an example to understand the key challenges facing the development of HII, how the challenges are interrelated, and how they can be met as a whole. Following a mixed methodology, involving workflow study, focus group discussions, and in-depth interviews, the study examines “data friction” along technical, institutional, regulatory, and legal dimensions. This study constitutes one of the first efforts to comprehensively investigate health information infrastructure and how technology and other dimensions in infrastructure are interrelated. The study therefore contributes to a better understanding of HII and the practical challenges that hinder the seamless flow of information in the healthcare environment.