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Both the southeastern Massachusetts region and the profession of nursing were developing in the 1960s. The need for a baccalaureate program in nursing came to the attention of local legislators and, in 1966, a bill was introduced in the state legislature to establish such a program at UMass Dartmouth's predecessor school, Southeastern Massachusetts Technological Institute. The Advisory Committee to the Board of Higher Education endorsed the program in 1967. The College of Nursing was established in 1969 with Sister Madeleine Clemence Vaillot as the first dean. Two departments were established: the Department of Adult and Child Nursing and the Department of Community Nursing.

The undergraduate program received initial accreditation from the National League for Nursing in 1973 and has been continuously accredited since. In May of 1977, Dr. Joyce Passos was appointed as the second dean, and the college grew. She expanded the basic program to allow for a flexible path for Registered Nurse students, broadened the mission beyond teaching to include scholarship and service, and expanded the community-based focus of care. A graduate program in nursing was established, currently offering three options: Adult Health Clinical Specialist or Nurse Educator (AHN); Adult Nurse Practitioner (ANP); and Community Health Clinical Specialist & Nurse Educator (CHN). The graduate program was approved in 1987 and received initial accreditation from the National League for Nursing in 1993.

In 1986, the Theta Kappa Chapter of Sigma Theta Tau was established. This chapter has won key awards for its outstanding work related to chapter goals.

In 1993, Dr. Elisabeth Pennington was appointed as the third dean. Under her direction, the faculty were encouraged to embrace change, knowing that quick response to a changing world was necessary. The college's mission and goal statement was revised, and the philosophy refined. In spring 2005, Dr. James Fain was appointed dean. He brought to the position experience as a nurse, nursing educator, nurse researcher, and administrator. In 2008, the college admitted its first cohort of PhD students to an innovative program of study that addresses the nursing faculty shortage and advances nursing knowledge in the care of people with chronic illness.

The college serves as the administrator of the University Lead Poisoning Education Project. This project, which is federally and state funded, educates, inspects, and supports lead abatement processes. The college also oversees the Gerontology minor and certificate programs.

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