From 1914 to 1916, it broke with the Socialists and entered legislative elections solely alongside other 'national' (non-regionalist) republicans though the electoral failure of 1916 put an end to this bloc.

The Radical Republicans generally supported the original constitutional bill that provided for an integral, unitary state but with allowance for devolved regions.

These disagreements led the two PRR ministers, Lerroux and Martínez Barrios, to quit the Azaña government in December 1931, and the Radical-Republicans would act as the principle opposition group.

The government proved unable to command sufficient confidence in the Cortes, with the result that snap elections were held in which the PRR emerged the strongest single group in parliament with 102 deputies.

Over the next year various governments dominated by Radical-Republicans were toppled before the cabinet was finally extended to include the CEDA, a move that prompted the October Rising of 1934.

The increasing preference of Lerroux's wing to cooperate with the religious right over the fellow secular Radicals of the republican left caused concern among many members of the party.

This led to the downfall of Lerroux as premier, though members of the PRR itself remained in the subsequent cabinets headed by two independents considered to be philosophically close to Radical-Republicanism, Joaquin Chapaprieta and Manuel Portela-Valladares.