In summer 1952, the Soviet secret police handed over the Lindenstrasse site to the Ministry for State Security (Stasi) of the German Democratic Republic. The Stasi operated the remand prison for the Potsdam district at this location until 1989. In 37 years, more than 6,000 people were imprisoned in Lindenstrasse, including 1,000 women.

Disorientation, isolation and round-the-clock surveillance were part of the daily routine for Stasi political prisoners. This was also evident from the structural changes that were undertaken at the prison from 1952 onwards: cell windows were sealed with glass bricks, and a block of five open-air (roofless) cells was built in the prison yard in the mid-1960s. The washbasins and toilets that visitors can see today were not installed until the mid-1970s.

Former prisoners report of interrogations taking place at all times of the day or night, cell lights left on permanently, continuous surveillance through spyholes in the doors, stringent rules of conduct and harassment by warders. Being on remand often meant solitary confinement. As a rule, prisoners were transferred to double cells only once investigations were deemed completed by Department IX (central investigation department) and interrogations were therefore over.

The criminal charges and reasons for arrest changed over time. In the early 50s, those most at risk of arrest were either alleged or actual political opponents. The most common charges in this period were for spying, sabotage, underground activities and antidemocratic propaganda. The waves of suppression that followed the popular uprising on 17 June 1953 and the building of the Berlin Wall in 1961 led to increases in the number of arrests. From the mid-60s onwards, the crime of defection was the main focus of political prosecutions. Almost 2,000 people were held on remand in Lindenstrasse following failed escape attempts or for aiding and abetting flight from the Republic. In the 1980s, there was a significant rise in the number of arrests of applicants for emigration. Inmate numbers reached an all-time high in 1988 and 1989. The nationwide amnesty for political prisoners in the German Democratic Republic on 27 October 1989 put an end to imprisonment for political reasons in Lindenstrasse.