But as a presidential hopeful in a party dominated by conservatives, the Tennessee Republican also voted for changes aimed at derailing the bipartisan compromise he helped forge.
"It's moving in the right direction," he said recently, a noncommittal answer that reflects a political straddle on one of the most complex and emotional issues to come before the Senate in years.
"No matter how he votes, people will question it," wondering whether presidential politics or some other factor determined his decision, said Sen. Trent Lott, R-Miss., Frist's predecessor as party leader.
Democrats applaud Frist for presiding over a lengthy, detailed debate, a rarity in an era of persistent partisanship.
"Certainly I want to give him credit," said Illinois Sen. Dick Durbin, who said Frist has set the stage for the second-ranking Democrat. At the same time, he said Frist's "personal position on this is hard to follow. I can't explain that other than to say he has set the stage for an honest debate."
Across the past week, Frist has voted to uphold some key elements of the bill, yet also sided with conservative critics at other points.
Most crucially, he voted to preserve provisions giving millions of illegal immigrants a shot at citizenship and upholding a new guest worker program.
On the other hand, he supported an amendment by Sen. Johnny Isakson, R-Ga., to make all other immigration changes contingent on a declaration that the border was secure, a provision that the bill's supporters said would have unraveled their coalition.
Frist was part of a 50-48 majority to make it impossible for guest workers to petition for citizenship on their own. The bill's supporters won a reversal the next day — over his opposition.
Ironically, Frist's handling of the immigration issue suggests a level of political dexterity that often has seemed lacking in a trained heart transplant surgeon who entered politics scarcely a dozen years ago.
Even some fellow Republicans cringed last year when Frist injected himself into the case of Terri Schiavo, the irreversibly brain-damaged Florida woman whose condition fused a controversy out of medical science, religion and politics. The majority leader viewed a videotape of the woman, then publicly questioned her doctors' diagnosis. An autopsy later confirmed their judgment, not his.
Frist drew additional unwanted attention last year when the Securities and Exchange Commission launched an investigation into the sale of stock in HCA, the hospital chain founded by his father and brother.
Frist has denied any wrongdoing, but even his allies concede privately the issue has cast a pall over his hopes for the White House. Ironically, Frist decided to shed the stock as he was getting ready for a possible run for the presidency, according to these allies, who spoke on condition of anonymity, after spurning advice to do so years ago to avoid just the sort of high-visibility embarrassment he's experienced.
On immigration, it's not only Frist's votes that seem designed to split the difference. Bush favors what he calls a "comprehensive approach" that includes border security, a guest worker program and a chance for millions of illegal immigrants to become citizens. GOP critics call that amnesty, and favor elevating border security above all else.
Frist's formulation? "Border security first, foremost. We've got to do it as part of a comprehensive plan," he told reporters recently.
The bill is likely to pass this week, possibly with more Democratic votes than Republican support. And Frist's own course has been circuitous.
In April, he gave the Senate Judiciary Committee a deadline for producing a bill. It did, and included a provision allowing illegal immigrants who came to the United States before 2004 to remain here.
The legislation "goes too far in granting illegal immigrants with what most Americans will see as amnesty," he said, and before debate could start, he made a gesture to conservatives. He introduced his own bill, essentially a border security measure.
Democrats quickly accused him of planning to hijack the proceedings. He did not, instead, making sure the bill lacked 60 votes, the total needed to overcome any filibuster. Next, he and aides worked with Sen. Arlen Specter, R-Pa., chairman of the Judiciary Committee, as well as Sens. John McCain, Chuck Hagel and Mel Martinez, on a change that was less generous to millions of illegal immigrants.
The effect was to push the bill slightly to the right without alienating Democrats who had voted for the committee measure, and pressure Senate Minority Leader Harry Reid to agree on a bipartisan compromise.
The two leaders joined a triumphant news conference where Frist characterized the developments as a "huge breakthrough," but avoided an outright embrace of the bill.
Compromise turned to combat with Reid, who wanted to limit the ability of Republican conservatives to propose amendments that would confront Democrats with politically difficult votes, and also sought assurances that any Senate bill wouldn't be rendered unpalatable in final compromise talks with House conservatives.
After a two-week congressional break in which the two leaders exchanged barbs, Frist made another gesture to conservatives. He arranged for $1.9 billion to be added to a spending bill to help with border enforcement.
Reid ultimately agreed he would not object to Republicans seeking numerous changes, Frist made concessions to satisfy the Democrats' other demand, and Republican conservatives agreed to whittle their stack of amendments. By Tuesday, they had proposed more than a dozen.