He played the role of Rémy, the main character, who is dying of terminal cancer, in the Canadian film Les Invasions barbares (The Barbarian Invasions) by director Denys Arcand. This film was awarded the 2003 Academy Award for best foreign picture. Arcand's earlier film Le Déclin de l'empire américain (The Decline of the American Empire) revolved around the same characters who appear 17 years later in Les Invasions barbares. Girard also appeared in Arcand's 1989 film Jésus de Montréal.
Girard is the most-nominated actor in the history of the Genie Awards. He has won the Leading Actor award twice, for Amoureux fou and Les Invasions barbares, the Supporting Actor award twice, for Jésus de Montréal and Les Portes tournantes, and has garnered three other nominations, for Le Déclin de l'empire américain, La Florida, Les Boys (all four movies and the TV series), Séraphin: Heart of Stone, and Aurore.
Girard also hosted a former game show called La Chasse aux Trésors that aired on Quebec television network TVA during the late 1990s. Girard played notorious criminal Lucien Rivard in a film called Le piege americain. Girard stars also as Hervé Mercure in the thriller 7 Days, directed by Daniel Grou. Girard also stars in the 2011 Canadian action comedy InSecurity on CBC Television.