The shoe missed its intended target and the man was arrested along with two accomplices, radio reports said.
The incident took place in the northern city of Thessaloniki where the prime minister was attending the opening of an international exhibition.
The 49-year-old assailant told reporters he was a radiologist and member of an ultra conservative organisation. He said he threw the shoe in protest at government fiscal and labour reforms.
The austerity measures were introduced in a bid to get the budget deficit down from around 14 percent of gross domestic product to under the EU-mandated limit of three percent by 2014.
Greece was saved from default in May by fellow euro area members, which agreed to lend it 80 billion euros over three years in return. The International Monetary Fund (IMF) added 30 billion euros.
Unions and other organisation have a called a demonstration in Thessaloniki Saturday evening to protest the government’s policies.