He organized bands of armed slaves, hired thugs and gladiators in opposition to Clodius, who supported Pompey's rival, Julius Caesar, and the Populares.
Milo became praetor in 54 BC, and in that year, he married Fausta Cornelia, daughter of the dictator Lucius Cornelius Sulla, and the ex-wife of Gaius Memmius.
In 53 BC, Milo made a bid for one of the consulships of the following year (he ran against Quintus Caecilius Metellus Scipio and Publius Plautius Hypsaeus, nominees of Pompey, who were running together) while Clodius was standing for the praetorship.
Conflicting stories claim that Clodius was either peacefully heading to Rome after receiving news a friend had died or lying in wait for Milo.
Whatever the reason, a scuffle led to a fight between the two parties, with Clodius being wounded by one of Milo's men (an ex-gladiator called Birria).
Milo returned to Rome and, with the aid of the tribune Marcus Caelius Rufus, he tried to swing popular opinion round to his side again.
On 22 January Milo tried to obtain an interview with Pompey at his house on the Pincian, apparently with a positive suggestion to improve the situation by withdrawing his candidature.
The Senate took action and passed the consultum ultimum (the ultimate decree), urging the interrex, the tribunes and Pompey to take steps to protect the Republic.
Milo wrote back that it was lucky for him that the same speech had not been made in court because otherwise, he would "not now be enjoying the delicious red mullet of Massilia".
[5] In 48 BC, Milo joined Marcus Caelius Rufus in the rebellion against Caesar, but he died at that year's siege of Compsa, near Thurii, in Lucania.
Titus Annius Milo appears as a recurring character in John Maddox Roberts' SPQR series of novels.
Milo also appears as a character in A Murder on the Appian Way, Last Seen in Massilia and A Mist of Prophecies, in the Roma Sub Rosa series of historical mystery novels by Steven Saylor.
Milo appears in Conn Iggulden's book The Field of Swords, the third in the series Emperor, as a street gangster who wages a private war with Publius Clodius.