Khlustinskaya charitable institutions appeared thanks to the initiative of Major Anton Semyonovich Khlustin, a landowner from Mosalsk. In 1802, he began constructing a house for the disabled and the insane, spending 50 thousand rubles in banknotes. His sons, Mikhail and Semyon, completed the construction in 1809, adding a church in the name of Alexander Nevsky, and handed everything over to the Public Charity Office, donating an additional 11.5 thousand rubles. This house became the foundation for future hospital institutions known as Khlustinskye.

By 1824, the complex included seven stone buildings, one two-story and six single-story wooden ones. In the same year, merchant I.M. Zolotarev donated a two-story stone house for the city hospital, investing 50 thousand rubles. This house, known as the 'Zolotarev Hospital House,' became part of the Khlustinskye institutions.

In 1834, the main hospital building was constructed, where the hospital was relocated from the Zolotarev house, and the house itself became a shelter for the insane. In 1869, the Khlustinskye institutions came under the management of the Kaluga Provincial Zemstvo, which accepted 514 patients and 140 thousand rubles in capital. The Zemstvo continued to improve and expand the institutions, creating a library at the hospital and replenishing the medical library. In 1888, the hospital church was renovated, and in 1895, the expenses for the institutions amounted to 117,147 rubles.

In 1874, a paramedic school with a three-year course was opened at the hospital, located in the house that became available after the relocation of the disabled. The school was allocated 7 thousand rubles per year, and over 14 years it graduated 104 paramedics. The school closed in 1888 but reopened on October 20, 1905, for students from the Kaluga province with a three-year course, and for midwives, a four-year course.

History has preserved the names of benefactors and doctors, such as Vasily Alekseevich Krasintsev, who headed the surgical department from 1893. At his initiative, a surgical building was constructed, an X-ray room was opened in 1913, and a tuberculosis dispensary in 1914. The senior physician was Vladimir Egorovich Krichevsky, the initiator of the creation of the Society of Kaluga Doctors in 1862.

The 1917 Revolution disrupted the funding of Khlustinskye institutions, but the hospital survived despite the difficulties. By the time of the formation of the Kaluga region, the hospital consisted of nine buildings and was staffed by 270 employees, including 14 doctors. The staff grew vegetables on 78 hectares in Romodanovo to support the hospital.

The inpatient facility with 400 beds included 130 surgical beds, 55 therapeutic, 135 infectious, 30 dermatovenereological, and 20 pediatric. There were plans to expand to 500 beds and open new departments.

Today, Khlustinskaya Hospital employs 860 staff, including 189 doctors and 435 nurses. Annually, 124 thousand patients are treated here. The hospital has a diagnostic service and two inpatient buildings with 215 beds, and it serves as a clinical base for the medical faculty of KGU. Since 1809, the hospital has had the church of Alexander Nevsky on its premises.