Vince Vaughn and Reese Witherspoon will star in New Line’s holiday comedy “Four Christmases,” set up at Spyglass with Gary Barber, Roger Birnbaum and Jonathan Glickman producing.

Vaughn’s also producing and Witherspoon’s in negotiations to produce the pic, in which a couple struggle to visit all four divorced parents on Christmas Day. Script’s penned by the writing team of Matt Allen and Caleb Wilson.

New Line execs are meeting with directors and eyeing a late fall start of production. That would give the mini-major a shot at getting “Four Christmases” into theaters during next year’s holiday season.

Both thesps have worked with New Line previously. Vaughn scored a break-out success with 2005’s “Wedding Crashers”; Witherspoon, who won the Best Actress Oscar for “Walk the Line” last year, recently wrapped on political thriller “Rendition,” set for an October release.

Vaughn will next be seen in Warner’s holiday comedy “Fred Claus” and next year’s Picturehouse release “Vince Vaughn’s Wild West Comedy Show: 30 Days and 30 Nights — Hollywood to the Heartland.”