The United Nations (UN) Court rejected his appeal against 2017 convictions for genocide, war crimes and crimes against humanity.
"The final judgment in the case against Mr. Ratko Mladic, who is one of the highest-ranking officials to be tried by the International Tribunal for the former Yugoslavia and by the Residual Mechanism, is a reflection of the international community’s commitment to international criminal justice and the fight against impunity," said UN Secretary-General Antonio Guterres in a statement on Tuesday.
Known as "the Butcher of Bosnia", Mladic presided over some of the most horrific crimes to occur in Europe since the Second World War.
He commanded violent ethnic cleansing campaigns across Bosnia and Herzegovina from 1992 to 1995, including the July 1995 massacre of thousands of Muslim men and boys in Srebrenica.
"It is another vital step towards coming to terms with the past to build a more resilient, secure and hopeful future for all citizens and residents of Bosnia and Herzegovina and the region," he stated.