With around half the votes counted, Renzi - the clear favourite in the race - has secured around 70 per cent of the three million ballots cast.
"A very large victory for Matteo Renzi is on the horizon, particularly in the major regions, he will have a very significant democratic mandate, and a very significant responsibility," said the former trade unionist Guglielmo Epifani yesterday, with around half the results in from yesterday's voting.
Organisers had expected turnout to be lower than for the PD's primary in 2009 when Pierluigi Bersani was elected leader, given Italians' growing disenchantment with politics.
Bersani had to step aside at the height of Italy's leadership crisis following inconclusive February elections, and the party elected union boss Guglielmo Epifani as its temporary leader in May.
But Letta praised the strong turnout, saying it meant the Democratic Party was a "bastion against rising populism".
Two other candidates ran against 38-year-old Renzi: Giuseppe "Pippo" Civati, also 38 and reform-minded, and Gianni Cuperlo, 58, a party apparatchik who is considered further to the left than the other two.
Renzi has vowed to overhaul the PD, which has roots in what was once Europe's largest communist party.
Little known until he challenged Bersani in last year's primary, Renzi has been riding high in the popularity sweepstakes even on the right.
The youthful Renzi has also long campaigned against the middle-aged leadership of his own party and pushed for a more centrist programme, although leftist critics accuse him of being thin on concrete proposals.
His supporters say that if Renzi had won against Bersani for the party leadership in 2012, the PD would have won handsomely in the February general elections.
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