US air strikes have been blamed for many civilian deaths
Afghan President Hamid Karzai has said about 40 people were killed in a US air strike in southern Kandahar province.
Many more were wounded when a wedding party was hit. US officials confirmed civilian deaths and are investigating.
"We cannot win the fight against terrorism with air strikes," Mr Karzai said in comments directed at US President-elect Barack Obama.
Mr Karzai has repeatedly criticised the high level of civilian casualties in such bombings.
The latest civilian deaths underline the challenges facing the US president-elect and future commander-in-chief.
The incident happened late on Monday evening in Shah Wali Kot district, a remote part of Kandahar province.
International forces had been involved in an operation against the Taleban - an air strike was called in but the missile struck a wedding party by mistake, killing as many as 40 people, women and children among them.
"My wounded son was in my arms, right here, bleeding," the father of the bride, Roozbeen Khan, told AFP news agency. "He died last night.
"I lost two sons, two grandsons, a nephew, my mother and a cousin."
Villagers said a wedding lunch had just ended when someone, perhaps a Taleban fighter, fired at international troops on a nearby hill, AFP reported. The soldiers returned fire and called in air support.
A spokesman for US forces confirmed there had been civilian casualties and expressed sorrow for what had happened.
An investigation is under way into what went wrong.
In a statement, Mr Karzai demanded an end to civilian casualties.
"My first demand from the US president, when he takes office, would be to end civilian casualties in Afghanistan and take the war to places where there are terrorist nests and training centres," he told reporters.
The BBC's Ian Pannell in Kabul says there may be little sympathy for the Taleban in many parts of Afghanistan, but there is even less sympathy for coalition forces when incidents like this leave innocent Afghans dead.
It is likely to loom large in the new relationship between Presidents Karzai and Obama when the new US administration is sworn in, our correspondent says.
Correspondents say that civilian casualties are hugely damaging to foreign forces trying to wage a "hearts and minds" campaign in Afghanistan.
The issue of civilian casualties is hugely controversial
Last month the US military said that air strikes on 22 August killed 33 Afghan civilians, many more than previously acknowledged.
And in another notorious incident, an Afghan parliamentary investigation in July found that a US air strike in the same month killed 47 civilians in the eastern province of Nangarhar.
Regional officials said those casualties were also attending a wedding party and that the bride had been killed.
Figures released in September by the United Nations said there had been a sharp increase in the number of civilian casualties - some caused by the coalition but most by the Taleban - in Afghanistan in 2008.
It said that from January to August 2008, 1,445 civilians were killed - a rise of 39% on the same period last year.