Jacques Servier, founder of the company that carries his name, was questioned by police from 10.30am until 6pm, according to newspaper Le Figaro.
His lawyer, Hervé Temime, announced he was being questioned over dishonest practices, deception over the drug's quality and of falsely obtaining authorization to sell it.
Mediator, originally a drug for overweight people with diabetes, was also prescribed as an appetite suppressant to people wanting to lose weight. Between 1976 and 2009 it was taken by over 5 million people.
Concerns about side effects emerged in 1999 when a patient in Marseille taking the drug was found to have heart-valve damage. Further heart-related problems emerged and the drug was eventually banned in 2009.
Estimates now suggest the drug could be responsible for between 500 and 2,000 deaths. Servier denies having misled authorities and patients.
"It's now up to us to explain ourselves," Servier's lawyer told journalists. "It goes without saying, but people who have been put on trial are innocent until proven guilty."
Servier had to post bail of €4 million ($5.4 million) and guarantee a further €6 million before December 15th.
The Mediator scandal is France's biggest public health scandal for years and has led to promises of reform in the way drugs are approved and greater transparency around possible conflicts of interest. In August health minister Xavier Bertrand promised "a radical and rapid reform."
The proposed reforms would require pharmaceutical companies to inform public bodies if a drug is withdrawn somewhere else in the world. France was slow to ban Mediator, which was never allowed for use in the US or UK and was banned in Spain and Italy in 2005.