Soon, Petrille turned states against the Lupertazzis and sent Sacrimoni to prison, leading to Leotardo becoming the new acting boss. He maintained a working relationship with the DiMeos, and Sacrimoni - still maintaining a working relationship with the DiMeos - had Soprano whack Millio and his soldier Eddie Pietro to put an end to their rebellion. However, tensions rose between the families after Leotardo killed DiMeo made man Vito Spatafore without permission due to his homosexuality. The DiMeos responded to this by blowing up the Lupertazzis' wire room in Sheepshead Bay, warning Leotardo.
Leotardo became boss of the family after Sacrimoni broke omerta with a guilty plea in the winter of 2006, and he refused to engage in a sitdown with Soprano, still angry about his brother's death at the hands of Soprano's cousin. Leotardo convened a war council with Albie Cianflone, Butch DeConcini, and Gerry Torciano, and DeConcini pushed hard to whack Soprano, while Leotardo was reluctant to whack a boss. Leotardo was hospitalized shortly thereafter when he suffered a massive coronary, and he returned to Brooklyn in late 2007 after undergoing heart surgery and several months of physical therapy. He found the family under the controversial leadership of Faustino Santoro, and he planned to make Torciano the new boss. However, Santoro had Torciano murdered at a dinner with DiMeo consigliere Silvio Dante. Soon after Sacrimoni died, and Carmine Lupertazzi Jr.'s decision to retire from the criminal lifestyle left no clear successor. Leotardo bided his time before having Butch DeConcini's enforcers whack Santoro on a city sidewalk.
War broke out between the Lupertazzis and DiMeos after an offer of compromise on an asbestos removal project was rejected, and after Soprano brutally beat Leotardo's man Salvatore Cogliano for threatening his daughter. Leotardo responded by putting out hits on Soprano, Silvio Dante, and Bobby Baccalieri, and Baccalieri was killed and Dante incapacitated. Soprano and Paulie Gualtieri later had a meeting with DeConcini, Cianflone, and Lupertazzi, who agreed that they were unhappy with Leotardo, and gave Soprano permission to whack him. Walden Belfiore executed Leotardo at a Raceway gas station, and DeConcini took over the leadership of the Lupertazzi family.