Poindexter accepted an athletic scholarship to attend the University of Virginia and he played safety for coach George Welsh's Virginia Cavaliers football team from 1995 to 1998. He was compared to NFL players, such as Ronnie Lott, for his hard-hitting style. As a redshirt freshman in 1995, Poindexter teamed with fellow defensive back Adrian Burnim in one of the most famous plays in Cavalier history as the two stopped Florida State's running back Warrick Dunn inches from the goal line, defeating the second ranked Seminoles 32-28. In 1996, he made a school record with 98 tackles and as a junior in 1997 he finished with 78. As a junior, Poindexter had the choice between declaring himself for the 1998 NFL Draft or staying in college for his senior year. Draft experts projected that he would likely be drafted in the first round, but Poindexter stayed at Virginia for his senior season but watched his draft stock plummet as injuries corrupted his senior season. The Cavaliers were expected to have a very strong team and were ranked as high as the top ten. In the first seven games of the season, Poindexter made 73 tackles, two sacks and three interceptions.