In the summer of 2005, Randolph declared himself eligible for the NBA Draft.
Randolph went undrafted in the 2005 NBA Draft, but on August 5, 2005, was signed to a free-agent contract with the Philadelphia 76ers. This contract did not guarantee him a spot on the 76ers' roster, but after participating in training camp, Randolph earned a roster spot.
Although he scarcely played in the early part of the season, Randolph took an expanded role with the team in late December 2005 after reportedly impressing other players and coaches in practices by being extremely hard working and good natured. Randolph posted season bests of 10 points and 13 rebounds.
Randolph broke his ankle on November 30, 2006, in an accident during practice that teammates described as gruesome, comparing it to former NFL quarterback Joe Theisman's career-ending injury.
On September 25, 2008, Randolph was signed to a non-guaranteed free-agent contract with the Portland Trail Blazers. His first game with the Blazers was played 38 games into the season, on January 14, 2009 against his former team, the Philadelphia 76ers. Randolph had 4 points in as many minutes. The Blazers did not resign Randolph in the 2009 off-season to make more room on the roster for the drafted players.
Randolph then joined the Miami Heat, but was waived by the team on December 14, 2009. He was signed by the Portland Trail Blazers on December 30, briefly waived, and re-signed to a ten-day contract. He was later signed by Miami again in the late part of the 2010 season. He was waived in October 2010.