At first, Mikloško's activities were limited to low profile organization of small student gatherings while working as a researcher at the Slovak Academy of Sciences.

However, since 1980s, Mikloško started gradually to contribute to organization of large religious pilgrimages, which has attracted the attention of the Communist regime.

In spite of the regime repression, Mikloško continued to organize increasingly anti-regime rallied, most prominently the Candle demonstration in Bratislava in 1988.

On 12 March 2008 František Mikloško, together with Vladimír Palko, Pavol Minárik, and Rudolf Bauer, established a new party called Conservative Democrats of Slovakia which was dissolved in 2014.

After 15 years, Mikloško returned to run for KDH ahead of 2023 parliamentary election.