This time he's poised to fare better.
Hayworth, a former congressman and talk-radio host, has given an alternative to conservatives frustrated with McCain's famous willingness to buck his party and work with Democrats on issues like campaign finance, immigration and climate change.
But McCain, who has never lost an election in his home state, has fought hard to cut into Hayworth's credentials as a conservative outsider.
McCain has spent $20 million to portray Hayworth as a big-spending creature of Washington and a late-night infomercial "huckster."
Hayworth registered briefly as a lobbyist and made $10,000 helping one client in 2008. And he lent his credibility as a former member of Congress to back up a Florida company's claims that it could help customers get thousands of dollars in free government grants.
McCain tossed aside his self-described "maverick" label and adopted a hard-line stand on immigration just a few years after working with Democrats on a path to citizenship for those in the country illegally. "Complete the danged fence," he says in a campaign ad, three years after dismissing the effectiveness of building a fence on the U.S.-Mexico border.
Hayworth has tried to keep the race focused on illegal immigration. He says McCain would support amnesty for illegal immigrants if re-elected — a charge McCain denies.
Hayworth has also called McCain a liar and a "shape-shifter," and he says he will pull off "an upset of proportions that the American people have never seen."
It would be quite the upset. Polls show McCain with a comfortable lead as high as 45 percentage points.