College friends step into the murky world of urban dating in “Significant Other,” an endearing romantic comedy by playwright Joshua Harmon that debuted Off-Broadway nearly two years ago. “S.O.” finds a second life at The Booth Theatre this season, with most of the original cast revisiting their former roles.

Harmon (“Bad Jews”) employs humor geared to millennials and moments particular to the wobbly lives of twenty-somethings—but his story, about how relationships change as we grow older, is universal.

At the center of “S.O.” is Jordan Berman (Gideon Glick), a gay, neurotic 29-year-old on the Upper West Side. His trio of besties are Laura (Lindsay Mendez), Kiki (Sas Goldberg) and Vanessa (Rebecca Naomi Jones). Jones is the sole new addition to the central quartet since the 2015 Roundabout production.

Also in the picture are Jordan’s ailing grandmother, Helene (multiple Oscar, Tony and Emmy nominee Barbara Barrie), and a couple of male utility players in multiple roles, which over time I’ve come to think of as “office beefcake” or “doofus fiancé.”

Jordan believes strongly in his friendships, and his tightest is with Laura. They’ve named the future children they’ll have if neither finds love with a more suitable partner, and they’ve come up with the perfect song for their wedding: “Because You Loved Me!” they both squeal, dripping with irony, in the romantic comedy’s first scene.

Glick (“Spring Awakening”) has fully realized his character, who is unsure, in a familiar way, if he’ll ever find an appropriate mate. His comic chops are put to fine use in a drawn-out scene where, late one lonely night, Jordan tries to rationalize sending a far-too-long e-mail to his office crush. One word for this performance? Relatable.

Mendez, the “Wicked” and “Dogfight” vet, keeps Laura grounded and full-of-heart, while letting us also glimpse the character’s countercultural and misanthropic sides.

With a nod to “Will & Grace,” Goldberg’s over-the-top Kiki is the Karen Walker of the bunch, delivering bon mots and generally telling it like it is. Jones is very good as a pessimist who admits at her own wedding that she has spent more time imagining her funeral.

For support, Jordan phones his grandmother, who is suffering from the early stages of dementia and who shares her darkest thoughts with her grandson. In Barrie’s irreverent performance is proof of how “S.O.” has improved with age. She and Glick share a bond that’s on display each time she asks him: “How’s your social life?”

Barrie’s earning deserved accolades for this role, and it’s because of her unsaccharine performance.

Raw emotional exchanges between the actors are explosive in the second act, where the story finds a climax at Laura’s wedding. There, all of Jordan’s anger and insecurities come out: “There are actually a lot of really good people in this world who never find someone, and I could be one of those people. … Then what happens to me?”

These actors have had time to steep in their roles, something we see manifest in silly, spastic, surprisingly well-choreographed dance sequences at assorted bachelorette parties. The piece ends in a sincere fashion, leaving most of Jordan’s questions about the future unanswered—as they may tend to be when you’re 29.

“Significant Other,” at The Booth Theatre, 222 W. 45th St. Tickets starting at $49, on sale through July 2. Call 212-239-6200.

Follow Robert Kahn on Twitter@RobertKahn