O'Driscoll, along with centre partner Luke Marshall, was concussed during last weekend's 13-13 draw with France, but both players have been passed fit for the trip to Rome on Saturday.
Jonathan Sexton was restored at fly-half having missed the last two matches against Scotland and France with a hamstring problem - but he was subsequently ruled out after having an injury he had picked up in training examined.
"A scan has confirmed that he has torn a tendon in his left foot and is therefore ruled out this weekend," read an Irish Rugby Football Union statement.
Paddy Jackson, who deputised in Sexton's absence, therefore retains his place while Ian Madigan has been restored to the bench.
Craig Gilroy returns on the right wing after overcoming a groin strain, replacing rib-fracture victim Fergus McFadden.
The pack is unchanged from the eight that started against France with lock Donnacha Ryan being given a clean bill of health after taking a bang on his shoulder at the Aviva Stadium on Saturday.
Substitute scrum-half Eoin Reddan fractured his leg against France, so uncapped Ulsterman Paul Marshall wins a spot on the bench that includes Devin Toner.
Openside flanker Simone Favaro has returned to the starting line-up in one of three changes for Italy.
Coach Jacques Brunel also brought in Lorenzo Cittadini in place of injured prop Martin Castrogiovanni and loosehead Andrea Lo Cicero will collect a record 103rd cap after replacing Alberto De Marchi.
Italy, who lost 18-11 to England at Twickenham on Sunday, are fifth in the table and hope to both avoid the wooden spoon by beating fourth-placed Ireland for the first time in the Six Nations.
Favaro takes the place of Robert Barbieri, who picked up a knock at Twickenham, and Castrogiovanni is still recovering from the muscle strain which forced him off during the England game.
Ireland team: 15-Rob Kearney, 14-Craig Gilroy, 13-Brian O'Driscoll, 12-Luke Marshall, 11-Keith Earls, 10-Paddy Jackson, 9-Conor Murray, 8-Jamie Heaslip (captain), 7-Sean O'Brien, 6-Peter O'Mahony, 5-Donnacha Ryan, 4-Mike McCarthy, 3-Mike Ross, 2-Rory Best, 1-Cian Healy
Replacements: 16-Sean Cronin, 17-David Kilcoyne, 18-Stephen Archer, 19-Devin Toner, 20-Iain Henderson, 21-Paul Marshall, 22-Ian Madigan, 23-Luke Fitzgerald
Italy team: 15-Andrea Masi, 14-Giovanbattista Venditti, 13-Gonzalo Canale, 12-Gonzalo Garcia, 11-Luke McLean, 10-Luciano Orquera, 9-Edoardo Gori, 8-Sergio Parisse, 7-Simone Favaro, 6-Alessandro Zanni, 5-Joshua Furno, 4-Quintin Geldenhuys, 3-Lorenzo Cittadini, 2-Leonardo Ghiraldini, 1-Andrea Lo Cicero.
Replacements: 16-Davide Giazzon, 17-Michele Rizzo, 18-Alberto De Marchi, 19-Antonio Pavanello, 20-Francesco Minto, 21-Paul Derbyshire, 22-Tobias Botes, 23-Tommaso Benvenuti.