Mexican drug kingpin Joaquin 'El Chapo' Guzman has pleaded not guilty to 17 separate charges in a New York court.
El Chapo was surprisingly extradited from Mexico earlier in the week and faces life in US prison if found guilty.
It will be alleged that he ran the world's largest drug-trafficking organisation during a decades-long criminal career.
The indictment carries a mandatory minimum sentence of life in prison, Robert Capers, the US attorney for the Eastern District of New York, said at a news conference earlier in the day.
US prosecutors have more than 40 witnesses ready to testify against Guzman, Capers told reporters, adding that the eventual trial will likely last "many" weeks.
Leading the Sinaloa cartel, Guzman oversaw perhaps the world's largest transnational cocaine, heroin and methamphetamine smuggling operation, playing a key role in Mexico's decade-long drug war that has killed over 100,000 people.
Guzman, 59, arrived in a small jet at Long Island's MacArthur Airport after nightfall on Thursday from a prison in the city of Juarez in the northern state of Chihuahua, where his Sinaloa cartel rules.