WBO Light Middleweight Championship
Margarito did face Daniel Santos in a rematch on September 11 of the same year, at the José Miguel Agrelot Coliseum in San Juan, for Santos' WBO world Jr. Middleweight title. The rematch also ended because of a headbutt, but this time, as the fight had already reached the four rounds mark needed for fights like these to be decided by judges, Margarito lost by a split ten round technical decision. He was down on two scorecards when the fight was stopped.On April 23, 2005, Margarito retained his WBO world Welterweight title against another Puerto Rican, undefeated world class puncher Kermit Cintron, dropping him four times on his way to a fifth round knockout. This was regarded as one of his best wins.
After almost a ten month layoff, Margarito returned to the boxing ring on February 18, 2006, retaining his title with a first round knockout of Jaime Manuel Gomez, who had lasted eleven rounds with Mosley for the IBF world Lightweight title eight and a half years before.
On December 2, 2006, Margarito defeated future champion Joshua Clottey by a twelve round unanimous decision. Margarito set a Compubox all-time record of 1675 total punches thrown in a twelve round bout.
