After the May Revolution proclaimed the self-rule of the country, Quiroga tried to enter the independentist army, and with this in mind, he travelled to San Luis to enter the Granaderos a Caballo Regiment, led by General José de San Martín, which was recruiting there, but he was imprisoned and eventually expelled due to his bad temper.
He moved back to La Rioja and became a businessman, until 1820, when the central government of Buenos Aires fell and the province became autonomous.
After the Brazilian war, the officers of the returning army (of centralist tendencies, known as unitarios) deposed the federalist governments in an attempt to restore the centralised rule of Buenos Aires. General José María Paz took over its province of Córdoba and his officers campaigned through the interior provinces. Quiroga tried to oppose them, but without success, and after defeat in the Battle of La Tablada, he went into self-imposed exile in Buenos Aires. From there, where the coup was quickly defeated, Quiroga led an army towards Córdoba but was defeated in the Battle of Oncativo by Paz's more disciplined forces. Quiroga decided not to give up and tried a more ambitious attempt, marching through territories still occupied by native aboriginals, in order to bypass Córdoba, and attack directly Mendoza, where it succeeded. He took his campaign north along the Andean provinces, until he finally defeated General Gregorio Aráoz de Lamadrid, who led the last remaining unitary forces, in Salta.
After the war, Quiroga established himself as one of the leaders of federalism in Argentina (along with Rosas and the caudillo of Santa Fe, Estanislao López), although he declared in his correspondence with Rosas that his ideas were in fact unitarian, but that he became a champion of federalism because people wanted federalism.
The political crime created a huge crisis in all the Confederation, forcing Maza to resign, and led to the establishment of Rosas' government. Rosas, as the Confederation leader, led the criminal investigation that ended with the prosecution of the governor of Córdoba José Vicente Reinafé, and his brother as the intellectual perpetrators of the crime. They were hanged along with Santos Pérez in Buenos Aires.
Today, some historians believe that the actual person responsible for Quiroga's death was Rosas himself, who used the crime to return to power. However, other historians state that there is no proof of that, and that Quiroga's death did not help Rosas at all.
In 1845, Domingo F. Sarmiento wrote Facundo, Civilization and Barbarism, a book that reviews the influence of caudillo leaders, which he defines as "barbarism", in the Argentine political and social life, but also as a protest to Rosas' regime, and a call for European education and life style.