Otsuka's U.S. roots began in 1985, with the Maryland Research Laboratories (MRL) (now OMML). MRL became the first tenant in the Shady Grove Life Sciences Center in Montgomery County, Maryland, near Washington, D.C., now the third largest center for life science companies and research in the United States.

By 1987, the organization had grown in size and scope, necessitating a relocation of clinical and administrative staff and the establishment of the Maryland Office of Clinical Research. In 1989, the company was incorporated as Otsuka America Pharmaceutical, Inc. (OAPI) to focus on commercialization of products in the U.S., and in 1999 launched its first Otsuka-developed product in the U.S., PLETAL^*.

In January 2001, the research and clinical development functions, which constituted a significant part of OAPI, was established as Otsuka Maryland Research Institute, Inc. (OMRI), a company focused on the research and clinical development of new healthcare products. And in 2003, MRL became Otsuka Maryland Medicinal Laboratories, LLC.

In 2007, OMRI merged with the Global Development & Commercialization division of OAPI to form Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC). OPDC is a globally focused organization that plays a leadership role in the research and development of Otsuka's ethical, innovative healthcare products.

When OPDC was established, OMML was incorporated as a separate organization.