AC Milan midfielder Montolivo, who was Italy's captain on the night, was hurt in a 15th minute challenge with Ireland defender Alex Pearce.
Early reports suggest Montolivo could now miss the World Cup as Italy's preparations continued with this stalemate against an Ireland side beaten 2-1 by Turkey in Dublin last weekend.
Italy, who started with Giuseppe Rossi up front as the Fiorentina striker sought to prove his fitness following a knee injury, dominated possession early on and had the first chance in the fifth minute.
Ireland goalkeeper David Forde had to fully stretch to clear Claudio Marchisio's powerful 30-yard effort towards the far post.
Prandelli was forced to make his first substitution in the 15th minute with Alberto Aquilani replacing the injured Montolivo, who hurt his left leg after a challenge with Pearce.
Ireland created their first chance in the 21st minute with Anthony Pilkington's curled free-kick kept out by Italy goalkeeper Salvatore Sirigu.
A minute later, Torino defender Matteo Darmian, who was making his senior debut with the Azzurri, came close to breaking the deadlock but his diagonal effort went just wide.
Ireland continued to press forward and David Meyler's stinging drive from outside the area forced Sirigu to palm the ball over the bar.
In the 33rd minute, Sirigu made a superb save to clear Shane Long's close-range header from Aiden McGeady's cross from the left.
Prandelli made his second substitution before half-time with Marco Parolo replacing the injured Aquilani.
Ireland picked up where it left off after the re-start and twice had opportunities to score early in the second half.
Hoolahan fed Long in the box but his right-footed strike was saved by Sirigu. Seconds later, Pilkington's curled attempt flew inches wide.
Italy thought they had taken the lead in the 56th minute when Ciro Immobile got behind Parolo's pass and struck the ball past Forde only to see his goal disallowed for offside.
Prandelli brought on Antonio Cassano before the hour mark in the hope the Parma forward could make the difference.
In the 65th minute, Cassano spotted an unmarked Marchisio in the area and the Juventus midfielder wasted a great chance as he struck the ball straight at the keeper.
With 12 minutes remaining, Ireland came close to being rewarded for their efforts when James McClean's cross found substitute Stephen Quinn in the box and his right-footed shot hit the bar with Sirigu already beaten.
Italy pressed forward more aggressively in the last stages of the game but could not find the finishing touch and held on for a draw.