The scheme produced “staggering losses in excess of $1 billion,” said George L. Piro, the special agent in charge of the F.B.I. office in Miami. Leslie R. Caldwell, who leads the Justice Department’s criminal division, said that the $1 billion in fraudulent billings made the prosecution the biggest that the department had ever brought against individuals in a health care case.

“This was a whole network of people scratching each other’s backs, paying kickbacks and giving each other referrals,” she said. “It shows what people can do when they’re determined to put their hand in the Medicare pot.”

The indictments refer to other unnamed participants accused of taking part in the billing scheme, including doctors and pharmacists, and Ms. Caldwell said the Justice Department was continuing its investigation to determine whether additional charges should be brought.

With evidence of Medicare fraud growing, federal officials have created “strike forces” in Miami and eight other locations in recent years to better identify and prosecute suspects. They have also turned more frequently to data analytics tools to look for red flags. The effort has led to charges against 2,900 people in the last decade, with the fraudulent billings totaling $10 billion.

Ms. Caldwell said that in prosecutions like the one in Miami, “we’re getting better at focusing on the worst of the worst.”

Mr. Esformes has faced legal scrutiny before in Florida and Illinois over the operations of his nursing and assisted-living facilities. In 2006, he and his partners agreed to pay $15.4 million to settle a civil lawsuit brought by federal officials over accusations of Medicare fraud in the Miami area.

But prosecutors charged in the indictment announced on Friday that he continued the fraudulent billings even after that settlement, using intermediaries, shell companies and money laundering operations to disguise the scheme.