[6] The following year, she appeared as Abby McDeere opposite Tom Cruise in The Firm and in 1995 had another lead role alongside Kevin Costner in Waterworld.

[7][8] The next few years she had supporting roles in small films, including Office Killer, Monument Ave., and Sliding Doors; and in 1999 appeared opposite Hugh Grant in the British romantic comedy Mickey Blue Eyes.

[13] In July 2012, Tripplehorn joined the cast of CBS procedural Criminal Minds in season eight, replacing Paget Brewster's character Emily Prentiss.

[16] Tripplehorn has appeared in the independent films Little Pink House (2017), with Catherine Keener, and Gloria Bell (2018), starring Julianne Moore.

In 2020, she returned to television in the Hulu miniseries Mrs. America opposite Cate Blanchett, Sarah Paulson, Rose Byrne, Tracey Ullman and Margo Martindale.

[17][18] She was later cast in a recurring role in the HBO period drama series The Gilded Age starring Christine Baranski and Cynthia Nixon.