Tax inversions have been a political hot button issue in Washington for years.
The rules unveiled this week were the Obama administration's third effort to stop U.S. companies renouncing their American citizenship but they are only a temporary stopgap.
Formal legislation to overhaul U.S. tax rules would be needed to bring a permanent end to the practice.
"We have succeeded in making it significantly harder for companies to strike inversion deals and redomicile overseas," said U.S. congressman Peter Welch. "But we still need action in Congress."
With a U.S. presidential campaign looming later this year there is much uncertainty about what shape such legislation would take, making deals all the more difficult to strike.
Last year was a record for M&A and a bumper year for mega matches. Out of the $4.6 trillion in deals inked, the number of individual transactions that exceeded $30 billion in value was 18 compared with seven deals worth more than $30 billion in 2014, Thomson Reuters data showed.
But the consequence of greater consolidation is increased scrutiny by antitrust officials. That was exemplified on Wednesday by the U.S. government filing a lawsuit to stop Halliburton from buying Baker Hughes, arguing the combination of the No. 2 and No. 3 oil services companies would lead to higher prices in the sector.
The Justice Department and Federal Trade Commission (FTC), which enforce antitrust law, have filed lawsuits to stop an unusually high number of deals in the past 18 months. FTC officials are in court this week to block a merger betweenStaples and Office Depot.
"It isn't just the number of proposed deals that makes this a unique moment in antitrust enforcement; it's their size and their complexity," U.S. Attorney General Loretta Lynch said in a speech on Wednesday.
"This represents a remarkable shift toward consolidation and it presents unique challenges to federal enforcers in our work to maintain markets that serve not just top executives and majority shareholders, but every American."