"Neither the president nor I have any illusions that direct dialogue with the Islamic Republic will guarantee success," she said in remarks prepared for delivery. "But we also understand the importance of trying to engage Iran and offering its leaders a clear choice: whether to join the international community as a responsible member or to continue down a path to further isolation."
The speech to the Council on Foreign Relations comes as Clinton tries to retake center stage as the administration's top foreign policy voice after four frustrating, low-profile weeks during which a fractured elbow forced her to cancel two overseas trips and numerous meetings.
On Thursday, she heads off on an around-the-world diplomatic mission, her first travel abroad in more than a month.
Her diminishing presence abroad and at home, followed by her startling public criticism of the White House this week for delaying a key appointment, has prompted a flurry of speculation about whether her influence is waning inside President Barack Obama's Cabinet.
Even in her speech, Clinton's hard line on Iran echoes Obama's own toughened warning last week to the hard-line regime that it has until September to show progress on scaling back its nuclear ambitions.
"Direct talks provide the best vehicle for presenting and explaining that choice," Clinton said, adding that "the time for action is now. The opportunity will not remain open indefinitely."
Some foreign policy observers say Clinton has been long overdue in carving out her own diplomatic persona.
"Her role so far has been more in the field of public relations than in policy formation," said Reginald Dale, a senior fellow at the Center for Strategic and International Studies. "She is seen as glamorous and in many countries as a valuable symbol of the United States, but it is not at all clear that she has an in-depth influence on foreign policy."
"She needs to decide if she wants to be the administration's mascot or have an impact on actual policy," he said. "If she wants to have an impact, the speech may be a way of claiming her stake."
Clinton's frustration was perhaps evident Monday when in a rare fit of pique, she lashed out at the White House for failing to quickly nominate someone to lead the U.S. Agency for International Development.
In rather undiplomatic comments, Clinton criticized the White House vetting process as a "nightmare," "frustrating beyond words" and "ridiculous." She added that overly burdensome financial and personal disclosure requirements had led several candidates to withdraw.
And, in an unusually blunt description of an administration squabble, she allowed that she had "tried very hard" but had been denied permission by the White House to tell USAID employees that they would soon get a new boss.
The White House declined to comment on her remarks.
The unfilled UDSAID post Clinton complained about is considered critical to what she often refers to as "smart power," the combination of defense, diplomacy and development that the administration wants to guide its foreign policy.
"Smart power counsels that we lead with diplomacy, even in the case of adversaries or nations with whom we disagree," Clinton said in Wednesday's speech. "We cannot be afraid or unwilling to engage."
And she rejected suggestions that a willingness to talk shows weakness or naivete.
"The president and I believe that refusing to talk to countries rarely punishes them. And as long as engagement might advance our interests and our values, it is unwise to take it off the table," she said.
Clinton aides say she is eager to get back to what had been a busy pace of travel and events although they deny any rivalries within the administration's foreign policy team and reject suggestions she has been forced into a backseat role.
They note that she has had frequent and regular meetings at the White House with the president, pointing to private sessions with both Obama and Vice President Joe Biden in the Oval Office scheduled for just an hour after her speech on Wednesday.
But they acknowledge that she has chafed under the limitations imposed by her injury, which notably caused her to miss important multilateral conferences in Europe in late June and to be unable to accompany Obama to Russia last week.
Still the impression persists that she lost clout in her absence, as Obama traveled frequently in an elevated foreign policy role that some observers have described as "diplomat in chief."
Biden has also assumed an increasingly public role in diplomacy in Iraq and has waded into both the delicate Mideast peace process and into American relations with Iran. National security adviser James Jones has shaped his own high-profile presence, while a group of globe-trotting special envoys have pursued shuttle diplomacy from Jerusalem to Kabul.
Michael Mandelbaum, a professor of American Foreign Policy at the Johns Hopkins School of Advanced International Studies, said it is still too early, six months into the administration, to assess Clinton's influence.
"Every president always overshadows every secretary of state, that's just the nature of the beast," he said. "But a secretary of state carves out a niche by picking out an issue, or two or three, and taking it as his or her own. She hasn't yet done that, at least not yet."
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