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O'Driscoll turned in a virtuoso performance in a seven-try 46-7 win against the Azzurri - setting up first-half tries for Jonathan Sexton and Andrew Trimble and playing a key role in the fly-half's second after the break.
Aware that the Championship may well be won on points difference, Ireland set about squeezing all they could out of the tiring Italians and Cian Healy, Sean Cronin, Fergus McFadden and Jack McGrath all also went over.
It means that O'Driscoll - who won a world record 140th international cap - and co will head to France next week aware that victory in Paris should be good enough secure the title, such is their dominant points difference.
It will be O'Driscoll's last ever match for Ireland and after running out on home soil for the Men in Green for the last time, the 35-year-old is determined to secure a second winners' medal, having played a key role in the 2009 Grand Slam.
"Hopefully next week there's a performance and a championship in this team. We have to go to France with huge positivity," said O'Driscoll, who was named man of the match.
"It's one thing playing in this jersey but it's another thing altogether winning in this jersey, and we've built a good standard. We're capable of doing great things and we have to start next week by trying to win a second championship as this unit of players.
"It's been a huge part of my whole adult life and to leave here it's going to be hard. But it was a good way to leave it and hopefully we set ourselves up for next week.
"I've loved my time playing in this jersey. It had to come to an end at some stage and I'm glad I'm able to go out at home with a big win. It will only properly set in when I've had a bit of time."