The first outdoor National Basketball Association game was played between the Phoenix Suns and the Milwaukee Bucks on September 24, 1972, during that year's preseason. The Suns defeated the Bucks, 116–103.

In the mid-1990s Hiram Bithorn Stadium was planned to be the home of the yet-to-be-named Puerto Rico team, a charter franchise of the United League (UL) which was a planned third league of Major League Baseball (MLB).

The stadium hosted Major League Baseball's Opening Day Game in 2001, in which the Toronto Blue Jays faced the Texas Rangers in an American League match-up. However, 4,000 who bought tickets were turned away when the police determined the safe capacity of the park had been vastly exceeded.

It was the object of a major overhaul under the mayoral administration of Jorge Santini, before becoming the part-time home of the Montreal Expos of the National League in 2003 and 2004 before their move to Washington, D.C. as the Washington Nationals. The Expos played 20 "home" games across the two seasons as a result of poor attendance at their home Olympic Stadium in Montreal. Before Major League Baseball's announcement of the Montreal Expos' move to Washington, Puerto Rico and San Juan made an effort to lure the Expos franchise to the island territory permanently.

Hiram Bithorn Stadium hosted parts of the first two rounds of the 2006 World Baseball Classic. Pool C, which included the teams of Puerto Rico, Cuba, Panama, and the Netherlands, was played there. It also hosted Pool 2 of the second round of the Classic which featured Cuba, Puerto Rico, the Dominican Republic, and Venezuela, the top two finishers from Pool C and Pool D. Pool D games of the 2009 World Baseball Classic were played there between March 7 and March 11, 2009. The Hiram Bithorn Stadium hosted the 2013 World Baseball Classic with Puerto Rico, Venezuela, the Dominican Republic and newcomers Spain in Pool C.

In 2008, it served as the stadium for Atléticos de San Juan and Academia Quintana, two soccer teams in the Puerto Rico Soccer League, Puerto Rico's first-ever professional soccer league.

In 2010, Major League Baseball returned to the stadium, as the Florida Marlins faced the New York Mets in a three-game series during the regular season.

The Marlins were to play the Pittsburgh Pirates on May 30 and 31, 2016 in honor of Roberto Clemente Day. However, on May 6, 2016, it was announced that the Puerto Rico games would be postponed due to the Zika virus outbreak, and moved to Marlins Park.

The Cleveland Indians and Minnesota Twins played a two-game series at Hiram Bithorn Stadium on April 17 and 18, 2018. It is the first time since 2010 that a Major League Baseball regular-season game was played in Puerto Rico. Furthermore, the league announced in August 2019 that they would be returning for a three-game series in April 2020 between the Miami Marlins and New York Mets. This series was later cancelled as a result of the Covid-19 Pandemic.

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