The Astros defeated the Rays 4-3 on Friday night.
Romero's X-Rays were negative and he's expected to return to his duties as early as Tuesday. Until then, Clark will be in the box at third.
Clark, 45, was granted a four-game leave of absence earlier this week to return to his home in Tupelo, Mississippi for a family matter. Saturday will mark his first appearance at the Major League level since appearing in 93 games for the Astros in 1998.
Clark, a lifetime .264 hitter in 13 Major League seasons, notched seven doubles for the Astros that year. He retired from his professional career one year later while with Triple-A Albuquerque.
Clark guided the 2007 Double-A Corpus Christi Hooks to a 67-73 record one season after leading the team to its first Texas League Championship. He was also at the helm when the North Shore Honu took the Hawaiian Winter League title in 2006 and served as the manager for the 2007 Mesa Solar Sox of the Arizona Fall League.
In five seasons as a manager entering 2008, Clark had posted a .530 (368-326) winning percentage.
His 13 seasons in the majors included playing time with the Chicago Cubs, Kansas City Royals, and Pittsburgh Pirates.