On Dec. 21, 2000, more than three years after the original verdict, the Mississippi Supreme Court overturned the conviction citing prosecutorial misconduct. The court ruled that the state improperly tried Flowers for all four murders during his trial for the murder of Tardy alone. The justices also ruled that the prosecutor argued facts that were not in evidence.

On April 3, 2003, the state Supreme Court overturned Flowers' second conviction, again citing prosecutorial misconduct. The court again ruled that the state improperly tried Flowers for all four murders during his trial for the murder of Stewart alone. The court also found that the prosecutor argued facts that were not in evidence, including misstatements in closing arguments of the timeline of the case and of witness testimony.

On Feb. 1, 2007, the Mississippi Supreme court again overturned Flowers' conviction. This time, the court cited the prosecution's use of racial discrimination in jury selection, known as a Batson violation after a 1986 U.S. Supreme Court decision. The justices wrote that the third Flowers trial was "as strong a prima facie case of racial discrimination as we have ever seen in the context of a Batson challenge."

The Mississippi Supreme Court upheld the conviction on Nov. 13, 2014. Flowers' attorneys appealed to the U.S. Supreme Court, which sent the case back to the state Supreme Court. In November 2017, the state Supreme Court once again upheld the conviction, writing in a 5-4 decision that "[W]e have determined that each issue raised by Flowers is without merit." More appeals are pending.