DENVER, USA (AP) - President Barack Obama and Republican Mitt Romney come face to face for the first time in this presidential campaign Wednesday night for a nationally televised debate that will give millions of Americans a chance to size up two fierce competitors in a moment of high-risk theatre.

Romney, trailing in polls in a number of key states and running short on time to reverse his fortunes, is angling for a breakout performance in the three 90-minute presidential debates scheduled over the next three weeks.

Obama, well aware that the remaining five weeks of the race still offer enough time for tectonic shifts in his prospects, is determined to avoid any campaign-altering mistakes as he presses his case for a second term.

A pre-debate skirmish Tuesday over Vice President Joe Biden's passing reference to "a middle class that has been buried the last four years" demonstrated how just a few words can mushroom into something larger during a heated contest for the White House.

Wednesday's 9:00 pm EDT face-off between Obama and Romney on domestic policy at the University of Denver is sure to offer a blend of choreography and spontaneity: Both men have spent hours rehearsing smart lines and pithy comebacks with proxy opponents - yet know to expect the unexpected.

"That's what so tricky about this," says Alan Schroeder, author of a book on presidential debates. "There's never a template for preparing because each one takes its own direction."

The central role of the economy in this election is evident in the topics selected for the first three of the night's six debate segments: The Economy I, The Economy II and The Economy III. The last three segments will focus on health care, the role of government and governing.

Romney has pinned his campaign on the argument that Obama has failed to adequately juice up the US economy, but his challenge is reflected in recent polls showing growing public optimism about the economy and the president's leadership. His case got tougher after a secret video revealed Romney telling donors that it's not his job to care about the 47 per cent of Americans who don't pay federal income taxes and believe they are victims.

Romney tried to address accusations that he doesn't care about those voters with a new ad Wednesday in which the casually dressed candidate looks at the camera and acknowledges the struggles of Americans living paycheque-to-paycheque. "We should measure our compassion by how many of our fellow Americans are able to get good-paying jobs, not how many are on welfare. My economic plan will get America back to work and strengthen the middle class," he says.

Romney calls Wednesday's debate the beginning of a month-long "conversation with the American people," and the debates do tend to consume much of the political oxygen for several crucial weeks.

The candidates will be speaking to a TV audience of tens of millions in one of those rare moments when a critical mass of Americans collectively fix their attention on one event. Fifty-two million people tuned in to the first debate four years ago, and 80 per cent of the nation's adults reported watching at least a bit of the debates between Obama and Republican John McCain in 2008.