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In accordance with Presidential Decree 742, the Administrative Order No. 278, s. 1976 was signed into law on February 12, 1976. It provided for the organization and activation of the Regional Health Office XII.
Until 1989, the office's mandate was based on Executive Order 119, which provided the Department of Health the sole responsibility in the formulation, implementation and coordination of policies and programs in the field of health. With the advent of Devolution, the DOH function on service delivery was devolved/transferred to the Local Government Units, Section 52, IRR of the Local Government Code of 1991.
The Department of Health underwent reengineering of its structure and functions, based on Executive Order No. 102, signed on May 24, 1999 by then President Joseph Estrada. It provided for the redirection of the functions and operations of the Department of Health.
The first phase of reengineering started at the DOH-Central Office where workforce was cut by 50%. Most of these staff were deployed and reassigned to various Regional Health Offices and retained facilities in the country. The second phase of reengineering, (for various regional health offices) was fully implemented on August, 2013 per Executive Order 366 or otherwise called “Rationalization of Government Agencies”. The Regional Health Offices are now called "Centers for Health Development" as reflected in the General Appropriation Act of 2001. Out of Two Hundred Thirty One (231) plantilla positions with One Hundred One (101) warm bodies, Sixty Three (63) personnel availed to retire and Fifteen (15) are co-terminus with the incumbent (CTI’s). Presently, there are One Hundred Thirty (130) plantilla position.

On March 18, 2014, per Regional Memorandum No. 054 s. 2014, the Center for Health Development-SOCCSKSARGEN has been changed to Department of Health-Regional Office No. XII.