Mitt Romney has taken a stride closer to the Republican presidential nomination by winning Wisconsin's primary, according to projections.
Exit polls also suggest he has won Tuesday's votes in Maryland and Washington DC.
A clean sweep would fuel calls for his main Republican rival, Rick Santorum, to bow out of the race in the name of party unity.
The eventual winner will face Barack Obama in November's election.
President Obama attacked Mr Romney earlier on Tuesday in the latest sign that he views the former Massachusetts governor as his November election opponent.
Former House Speaker Newt Gingrich and Texas Congressman Ron Paul trailed far behind Mr Romney and Mr Santorum in Maryland and Wisconsin, according to projections.
Exit polls indicated that voters were primarily concerned with a candidate's ability to defeat Mr Obama.
Although Mr Romney could not secure the nomination outright on Tuesday, analysts say he is close to a tipping point where Mr Santorum would be unable to catch him in the race.
Mr Santorum, who was not on the ballot in Washington DC, only seriously competed in Wisconsin, an agricultural and manufacturing American heartland state that was the night's biggest prize.
In a speech on Tuesday night, the former senator pledged to fight on to the primary in his home state of Pennsylvania on 24 April.
Mr Romney and his allies have spent an estimated $53m (£33m) on television advertising so far this election cycle, compared with $27m from his three Republican competitors combined.
He has been focusing his stump speech attacks on Democratic President Obama, who hit back on Tuesday.
Mr Obama launched a stinging critique of the budget proposal recently laid out by a high-profile Romney ally, Wisconsin congressman Paul Ryan.
Addressing news executives in Washington DC, President Obama said the so-called Ryan budget was "thinly veiled social Darwinism".
He also condemned Mr Romney for backing the budget proposal, saying: "He even called it marvellous, which is a word you don't often hear when it comes to describing a budget."
Mr Obama's re-election campaign is also running a new TV ad in six swing states criticising Mr Romney by name for the first time - in this case as a backer of "Big Oil."