After turning professional, Calderón was frequently showcased on
ESPN's
Friday Night Fights show. On July 1, 2001, Calderón defeated José Manuel Ramírez by unanimous decision. During this fight, he suffered an open wound over his right eyebrow, which required surgery. He had dropped Marquez twice before the end of the fight. Calderón retained his title by a 12-round decision in his first defense, on September 5, over Lorenzo Trejo of Mexico, at
Caguas, Puerto Rico. In his second defense, held at
Bayamón, he defeated former world champion
Alex Sanchez by a unanimous twelve-round decision. On March 20, 2004, he retained the championship with an eleventh-round knockout win over former
International Boxing Federation world champion Edgar Cardenas, in Guaynabo. Before that fight, Calderón obtained his high school credit diploma. On July 31, 2004, as part of the
Morales-
Hernandez undercard in Las Vegas, he retained his title once again, with a twelve-round decision win over former world champion Roberto Leyva. On November 23 of that year, he made his fifth defense, defeating
Nicaraguan Carlos Fajardo by a twelve-round unanimous decision. As part of the
Barrera-Morales III undercard. His fight with Fajardo was shown live on
HBO's
Pay per view. On April 30, of 2005, he retained the title with an eighth-round knockout victory over Noel Tunacao, a member of the Tunacao boxing family of the
Philippines. On September 25, he retained his title for the seventh time, with a twelve-round unanimous decision over Mexico's Gerardo Verde, at
Atlantic City, New Jersey. On December 10, 2004, Calderón retained the title again, this time with a twelve-round unanimous decision over former world champion Daniel Reyes. Calderón began 2006 by defending his title successfully on February 18, with a twelve-round unanimous decision over Isaac Bustos in Las Vegas. He would defend his title successfully twice in 2006 after his fight with Isaac Bustos. On April 29 against Miguel Tellez winning the fight by technical knock out thus gaining his sixth knock out victory. He finished his boxing year on October 21 by defeating
José Luis Varela of
Venezuela by unanimous decision. Following this fight the World Boxing Organization recognized him as a WBO Super Champion for reaching ten successful title defenses. On his first fight of 2007 that took place on March 28 in
Barranquilla,
Colombia Calderón defeated
Ronald Barrera by split decision. Following his fight against Barrera Calderón announced that he was interested in changing weight and challenge one of the champions in the light flyweight division thus finishing his minimum weight run after twelve successful defenses of the division's title. During this timeframe,
Freddie Roach selected Calderón as a sparring partner for
Oscar De La Hoya. The reason for this was that the trainer was seeking a fast adversary. On November 16, 2008, Roach rememorated the event in his blog for
The Ring, stating that "Calderon slapped Oscar around like it was unbelievable." The trainer also noted that he asked De La Hoya to pursue the offense, but the boxer's attempts were unsuccessful. In response, Calderón expressed that he participated in "three or four rounds" of sparring, during which he "gave him problems" and "made him uncomfortable", while De La Hoya "tried to hit" but seemed "out of timing". Similarly, Calderón competed against
Shane Mosley in a four-round sparring match. The session was in preparation, serving as training for the first of a series of fights against
Hugo Cázares. During the actual contest, Mosley had problems landing punches due to his adversary's speed. Calderón entered the ring accompanied by a display of fireworks, before a crowd that featured several media personalities, including Oscar De La Hoya. The size difference between both pugilists was evident since the moment that they stood next to each other prior to the beginning of the fight. During the course of the fight Esquer was more active offensively. During the first four rounds of the match Calderón used his boxing skills to avoid being hit by the punches thrown by Esquer. From the fifth round onwards Calderón proceeded to exchange combinations of punches with Esquer, eventually gaining control of the fight's tempo. The fight lasted twelve rounds and Iván won the fight by unanimous decision with the judges awarding scores of 116–112, 118-110 and 115–113. Calderón's second defense in the light flyweight division took place on April 4, 2008, where he defeated
Nelson Dieppa by unanimous decision. The three judges awarded him identical scores of 120–108. In the early stages, the fight's pattern was similar to the first meeting. Calderón relied on counter punching while boxing to avoid Cázares' offensive. Late in the first round, the challenger fell following a combination, but the referee declared that it was an accidental slip. In the following rounds, Cázares tried pressuring in the offensive, but Calderón continued boxing and held his opponent if approached. Due to the nature of this injury, the Puerto Rico Boxing Commission prohibited Calderón participation in any card within 120 days. Two weeks after the contest, the wound was reopened and he underwent plastic surgery to prevent reinjury. On September 23, 2008, Peter Rivera announced that Calderón was expected to return between January and February 2009. Rivera noted that the fight would be against one of the other light flyweight champions, most likely
César Canchila, citing that although both
Ulises Solís and
Edgar Sosa were approached, with both claiming to be available, neither one actually pursued serious negotiations. He subsequently stated that negotiations had been extended to Solís' representatives, but that those of Sosa still declined, citing that "[He] is a fighter that has always refused to fight with Iván. His managers don't want to sacrifice him and prefer to keep him in Mexico competing in soft fights." In the meanwhile, he received a homage as part of the Dominican Parade in San Juan, serving as
Padrino Internacional (lit. "International Godfather") along
Juan Manuel López. On June 13, 2009, Calderón defended the championship against
Rodel Mayol. During the second and third rounds, Mayol pressured the offensive, managing to land a moderate number of punches. In the fourth round, Calderón began pursuing the offensive, while avoiding Mayol's punches. This pattern continued during the following three rounds. In the fifth, Mayol connected his best punch of the fight, winning the round. To retaliate, Calderón became more aggressive, throwing more combinations. The seventh round began with exchanges from both boxers, but a head clash opens another laceration that stops the fight. The contest was declared a technical decision, with the judges offering scores of 68-65 twice for Calderón and 68-65 for Mayol. ==Retirement==