In 1748, the cathedral was abandoned after a major fire and the building was used for various other purposes. It was reconstructed in the Baroque style in 1785. The cathedral was once again destroyed by the Russian army during the Kościuszko Uprising.
19–20th centuries
In 1808, a local prelate sold the neglected building to the Vilnius University, which had the building thoroughly modernised in 1822 in the Neoclassical style by Karol Podczaszyński. After that, the building hosted an anatomical theatre, library and other university facilities for half a century.
St. Tikhon (Belavin), then Archbishop of Vilnius, presided over the cathedral and Orthodox Christians of Lithuania between 1913 and the occupation of Lithuania by the German troops in 1915. Most of the Russian Orthodox clergy left with the retreating Russian army.
The cathedral of the Theotokos was damaged during the Second World War but was restored in 1948, although its renovations were not completed until 1957. Today the cathedral belongs to the Russian Orthodox Church and was once again renovated in 1998. Its services are attended mostly by ethnic Russian and Belarusian residents of Vilnius.