In order to save the only medical program in the region, a group of lay and professional leaders in southern Puerto Rico acquired the school of medicine and established the independent Ponce Medical School Foundation, Inc. as a non-profit organization in January 1980.

In 1981, the Liaison Committee on Medical Education (LCME) accredited the school to grant the Doctor of Medicine degree.

A Clinical Psychology Doctoral Program (PsyD Program) was begun in 1999 which was later expanded to offer a PhD in Psychology, Professional Certificate in Couples and Family Therapy, and Postgraduate Certificate in Neuroscience of Learning.

On 5 September 2014, the Ponce School of Medicine and Health Sciences was acquired by Arist Corporation, which itself is an investment of global media, services and education company Bertelsmann.

[8][9] On 4 December 2014, Andreas Charalambous, executive dean of the University of Nicosia Medical School (UNMS), and David Lenihan, president and CEO of PHSU, signed an agreement to promote academic cooperation and collaboration in research.