In the mid-2000s, Grupo Episcopal San Lucas enlarged the facilities on Avenida Tito Castro and by the end of the decade it centralized everything on Avenida Tito Castro, vacating entirely the old structure on Calle Guadalupe.

Grupo Episcopal San Lucas also owned Hospital Cristo Redentor in Guayama until it was acquired by Sistema de Salud Menonita in 2017.

[8] Starting in the late 1920s, Puerto Rico experienced the development and building of public general hospitals intended to serve the health and medical needs of multiple neighboring municipalities.

In 1955, Hospital de Distrito moved to a new and larger campus located on the north side of Puerto Rico Highway 14 (aka, Carretera Central, and today -2015- Avenida Tito Castro) in barrio Machuelo Abajo.

[12] In July 2011, the hospital stopped honoring the Humana "Mi Salud" health care insurance plan on the grounds that it was unfair as compared to the payments made to the San Juan area hospitals.