Initial tracking for the film has the sequel earning north of $125 million upon its debut when it opens May 3.
Featuring Robert Downey Jr. as billionaire Tony Stark, the first number is slightly below the first weekend for 2010's "Iron Man 2" which earned $128.1 million.
Boxoffice.com projects the film to debut at $151 million.
Last year's Marvel superhero film "The Avengers" went on to earn a record-breaking $207.4 million last year in its premiere weekend at the box office.
The film will help turn around a dismal box-office year so far.
Currently,
Placing second is DreamWorks Animation's "The Croods" with $43.6 million.
"Iron Man 3" is the first big blockbuster set to debut next month with "The Great Gatsby," "Star Trek Into Darkness," and "The Hangover: Part III" opening in the weeks following.