Guzmán was sidelined for the entire 2006 campaign with a shoulder injury and subsequent surgery, but returned in 2007 as the Nationals' starting shortstop following the trade of second baseman José Vidro to the Seattle Mariners and the move of Felipe López to second base. However, he injured his hamstring on the first day of the regular season. He was on the disabled list until May 7, 2007. Batting leadoff, he was hitting .329 (second on the team), and despite missing almost half of the season through late June, was third in the league with six triples. On June 24, however, Guzmán was injured while tagging out a would-be base-stealer, and had surgery the next day to repair a torn thumb ligament, sidelining him for the rest of the 2007 season.