For the second time in two weeks, the United States has carried out airstrikes against a facility used by Iran’s Islamic Revolutionary Guards Corps and its proxies in eastern Syria, ratcheting up retaliation for a steady stream of rocket and drone attacks against American forces in Iraq and Syria.

The strikes by Air Force F-15E jets against a weapons storage facility came after U.S. airstrikes on Oct. 27 against similar targets in eastern Syria failed to deter Iran or its proxies in Syria and Iraq, which the Biden administration has blamed for the attacks.

Not only have the attacks continued — there have been at least 22 more since the American retaliatory strikes last month — but Pentagon officials said they have become more dangerous. Iran-backed militias have packed even larger loads of explosives — more than 80 pounds — onto drones launched at American bases, U.S. officials said.

“This precision self-defense strike is a response to a series of attacks against U.S. personnel in Iraq and Syria by I.R.G.C.-Quds Force affiliates,” Defense Secretary Lloyd J. Austin III said in a statement. “The president has no higher priority than the safety of U.S. personnel, and he directed today’s action to make clear that the United States will defend itself, its personnel, and its interests.”

“The United States is fully prepared to take further necessary measures to protect our people and our facilities,” he added. “We urge against any escalation.”

Biden administration officials have been trying to calculate how to deter the Iranian-backed Shiite militias from attacking American troops in the region without sparking a wider war, said three administration officials, who spoke on condition of anonymity to discuss internal planning.

“The attacks, the threats coming from militia that are aligned with Iran, are totally unacceptable,” Secretary of State Antony J. Blinken said in Iraq on Sunday.

The Pentagon said on Wednesday that there had been at least 41 attacks on U.S. forces in Syria and Iraq since Oct. 17 and that at least 46 U.S. service members had been injured, 25 of whom had suffered traumatic brain injuries.

In meetings to select targets, U.S. officials try to game out what response each strike will bring, one official said. Military officials at the Pentagon’s Central Command and in the American intelligence community have a good idea where many militia leaders are, two officials said, and have, in the past two weeks, considered the possible blowback if targeted airstrikes were to kill those leaders.

The effort to calibrate retaliation is inexact, the officials acknowledged.

The Biden administration also uses a “deconfliction” line with Russia to try to manage escalation in Iraq and Syria, two officials said. Russia has troops in Syria, and American officials say they expect that telling Russia before a strike in Syria is the same as telling Iran, as Russian officials often inform Tehran of what is coming.

Since Hamas’s surprise attack against Israel on Oct. 7, President Biden and his aides have sought to prevent the war between Israel and Hamas from spilling over into a regional conflict with Iran and its proxies in Lebanon, Syria and Iraq.

To that end, the United States has deployed one aircraft carrier to the eastern Mediterranean near Israel and another now in the Red Sea heading south, as well as dozens of additional warplanes to the Persian Gulf region. The Pentagon has also rushed additional Patriot antimissile batteries and other air defenses to several Gulf nations to protect U.S. troops and bases in the region.

Iran’s supreme leader, Ayatollah Ali Khamenei, has repeatedly pledged to destroy Israel and repel U.S. military forces from the region, and the leaders of militant groups in Yemen, Lebanon, Syria, Iraq and Gaza view Mr. Khamenei as a powerful ally, often seeking his advice and consulting with him on strategic issues.

Despite the often fiery rhetoric from Tehran, U.S. officials assess that Israel’s adversaries are not seeking a wider war.

“We assess Iran, Hezbollah, and their linked proxies are trying to calibrate their activity, avoiding actions that would open up a concerted second front with the United States or Israel, while still exacting costs in the midst of the current conflict,” Christine S. Abizaid, the leader of the National Counterterrorism Center, told a Senate panel last week. “This is a very fine line to walk.”

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