Paul Rudd, Romany Malco, and Seth Rogen play co-workers who resolve to help him lose his virginity, and Catherine Keener stars as Andy's love interest, Trish.

Watching Carell's performance in Anchorman: The Legend of Ron Burgundy (2004) inspired Apatow to cast him in the lead role for the film, and they wrote The 40-Year-Old Virgin together.

Critical reviews were generally positive, with praise for Carell's performance and the film's well-meaning yet bawdy humor, which was a point of contention by some conservative commentators as well.

Andy is mortified upon discovering the next day that everyone else at work has learned about the secret, including their boss Paula, who is attracted to him and later privately offers to take his virginity.

Jay drags Andy to various social events, books a painful chest waxing appointment, and sets him up with a prostitute, which all end with embarrassing results.

After Marla argues with Trish over wanting birth control, Andy takes her to a group information session at a sexual health clinic, where she is mocked for being a virgin.

As Cal takes on Andy's previous role, he hires a woman named Bernadette to work at the store, hoping to match her with David so he can move on from Amy.

Other cast members include Kat Dennings as Marla Piedmont, Mindy Kaling as Amy, Gerry Bednob as Mooj, Marika Domińczyk as Bernadette, Shelley Malil as Haziz, Mo Collins as Gina, Kimberly Page, Gillian Vigman, and Siena Goines as women attending the speed dating event, Nancy Walls as the health clinic counselor, Cedric Yarbrough, David Koechner, and Jeff Kahn as fathers attending the health clinic, Loren Berman, Nick Lashaway, and Julian Foster as boys attending the health clinic, Chelsea Smith as Julia, Erica Vittina Phillips as Jill, Jonah Hill as a customer at Trish's store, Jordan Masterson as Mark, Jazzmun as a prostitute, Miki Mia as the waxing lady, Denise Meyerson as Robin, Michael Bierman as a 16-year-old version of Andy, Lee Weaver as Joe, Kevin Hart, Wayne Federman, Ron Marasco, and Joseph T. Mastrolia as Smart Tech customers, Kate Luyben as a woman who purchases videotapes, Stormy Daniels as a porn star, Shannon Bradley, Brianna Brown, Elizabeth Carey, Elizabeth DeCicco, Hilary Shepard, and Barret Swatek as bar girls, Carla Gallo as a girl who sucks on toes, Laura Bottrell as a college girl, Joe Nunez as a man who buffs floors, Charlie Hartsock as the speed dating MC, Gloria Helena Jones as Sara, Marisa Guterman as a girl wearing braces, Matthew McKane as a motorist, Miyoko Shimosawa as a waitress, Rose Abdoo, Steve Bannos, and Brooke Hamlin as restaurant customers, Marilyn Dodds Frank as a woman who buys a television, and Loudon Wainwright III as a priest.

She also mentioned "you had to kind of lose sense of being self-conscious on that movie because it was sort of an all-in in terms of throwing a joke out or even the writer would sit behind the monitors behind the curtain".

[5] Production was halted by Universal Pictures after the first week, due to concerns that the physical appearance of Carell's character resembled that of a serial killer, and that the early footage was not funny.

He was surprised to find out his mother ended up taking "all of her church friends to see it, multiple times", and stated The 40-Year-Old Virgin "changed my career" by leading to more subsequent job offers without prior auditions.

Elsewhere, it opened with $66,277 in Argentina, $1,608,724 within Australia, $5,451 from Bulgaria, $25,200 in the Czech Republic, $29,884 within Lebanon, $310,280 from the Netherlands, $119,930 in Norway, $133,509 within Poland, $9,091 from Slovakia, $87,535 in South Africa, and $157,386 within Turkey.

This additional footage consists of more nudity, Andy asking Viagra for help on how to get rid of an erection, another scene featuring a "bad encounter" from his younger days, fantasies of a porn star, and Jay having "a lot more amusing racial banter" with Mooj.

[29] With an approval rating of 84% at the end of 2005, Rotten Tomatoes ranked The 40-Year-Old Virgin as the year's "Best Reviewed Comedy" and added it "proves that Steve Carell has the comedic chops to carry a movie and provide a good share of laughs.

"[31][32] The pair gave minor criticisms, with Ebert describing "the way she (Catherine Keener as 'Trish') empathizes with Andy" as "almost too sweet to be funny" and Richard Roeper saying that the film was too long, and at times extremely frustrating.

Club reviewer Nathan Rabin felt Carell made "a surprisingly graceful transition to a leading-man role" following his performance in Anchorman, and said both of them worked well due to the "chemistry and comic chops" of their casts.

He concluded by praising Carell for instilling "a good deal of complexity and sophistication into his affectionate characterization" and believed it compensated for a perceived lack of humor in the romance.

"[36] Emanuel Levy gave the film a B+ grade, calling it an R-rated comedy superior to Wedding Crashers that has "a generous heart and a sweet, almost naive center" in spite of the profane language used.

[37] While Brian Lowry of Variety believed The 40-Year-Old Virgin was slightly too long and "indulges in some juvenile excesses", he also felt it often provoked laughs even when "sophomorically homophobic.

She wrote Andy remaining "steadfastly chaste and genuinely humane" was its most surprising aspect and described him as a character "of old-fashioned decency in a movie that otherwise flouts it at every turn.

"[39] It was condemned by Harry Forbes of Catholic News Service as "relentlessly vulgar and frequently offensive",[40] and by political columnist Cal Thomas for being an example of societal decline in regard to "self-control or what was once known as purity.

The site's critical consensus reads, "Steve Carell's first star turn scores big with a tender treatment of its titular underdog, using raunchy but realistically funny comedy to connect with adult audiences.

[44] For the film's tenth anniversary, Erik Abriss from Complex and Josh Wigler of MTV News both wrote pieces asserting it remained enjoyable.

She wrote that the movie "launched (almost) a thousand bromantic comedies", put Apatow "on the mainstream map", and made him a "Hollywood king (and, much more interestingly, queen)-maker".

"[46] Chris Serico of Today said this "has continued to resonate among comedy fans, and served as a breakthrough movie for its director, Judd Apatow, and his co-writer/star, Steve Carell" a decade after being released.

[47] A 2018 article from Detroit Free Press contributor Julie Hinds noted that The 40-Year-Old Virgin was "Michigan's favorite romantic comedy", and called that ranking "a fine choice" when "Carell's character has a heart of gold" and "eventually lands in a solid, committed relationship".