Despite having the time of his life on True Blood, he has one lingering regret. He missed out on being cast as Superman by Zack Snyder for Man Of Steel, the reboot due for release in 2013.
"The director said I was down to the last two. It's heartbreaking," says 34-year-old Manganiello with a deep sigh, revealing he'd even had his measurements taken for the suit.
"As fate would have it, the show that got me noticed by Snyder was also the show that made it impossible for me to go off and screen test, because Superman overlapped with True Blood. Alan [Ball] made it clear they had big plans for my character and that they weren't willing to share me with Superman.
"I'll have a break in about 10 years," he says with a smile.
But every cloud has a silver lining and Manganiello was left free to film What To Expect When You're Expecting with Cameron Diaz, Jennifer Lopez and Chris Rock.
With no hard feelings for his Superman loss, the 6ft 5ins actor is throwing himself into work and werewolves again. He's well aware his appearance is a big part of the reason he landed the True Blood role.
"As soon as I started reading the scripts and saw the way my character was described, I thought, 'Man, I'm definitely going to be the piece of meat on this show'," he says.
At the end of series two, vampire Bill Compton, played by British actor Stephen Moyer, was kidnapped moments after proposing to his human girlfriend Sookie Stackhouse (played by Moyer's real-life wife, X-Men star Anna Paquin).
Sookie's now on a mission to get her lover back and employs reclusive werewolf Alcide to help search for him.
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