Members of an Afghan wedding party have been killed in a second air strike over three days, local officials say.
Witnesses said at least 20 civilians, travelling to the wedding in Nangarhar on Sunday, were killed. Women and children were among the dead and injured.
The US said the air assault was targeting fighters. It comes a day after at least 15 people were killed and seven injured in an air raid in Nuristan.
Captain Christian Patterson, the coalition media officer, said: "It was not a wedding party, there were no women or children present. We have no reports of civilian casualties."
The US-led force said in a statement earlier that "several" fighters had been killed.
One witness, Lal Wazir, whose tunic was covered in blood after carrying some of those wounded to hospital, said the attack came at about 6.30am (0200 GMT).
"The wedding participants were on their way to the groom's house," Wazir said outside the hospital.
"They stopped in a narrow location for rest. The plane came and bombed the area. There were between 80 to 90 people altogether.
"We have carried six of the injured to this hospital, and more might be coming. The exact number of casualties is not clear," he said.
A male survivor who escaped without injury, told Al Jazeera: "We saw the plane overhead and we heard the sound of the bombing.
"I asked one person to see what happened and he came back with an injured child. Then we went there ourselves and there were dead bodies everywhere."
James Bays, Al Jazeera's correspondent in Afghanistan, said the incident would cause deep concern for Hamid Karzai, Afghanistan's president, as it was the second time in two days that residents had reported civilian deaths at the hands of the US military.
"This latest attack claimed the lives of between 20 and 30 people. The Americans claim they were militants, but in the local hospital there are women and children."
The issue of civilian casualties has caused friction between the Afghan government and US and Nato troops, and has weakened the standing of Western-backed Karzai in the eyes of the population.
Karzai has repeatedly called for better co-ordination between Afghan and foreign troops in pursuing fighters in civilian-populated areas, and for international troops to cut down on civilian casualties.
Civilian deaths caused a huge outcry last year, but there have been fewer accusations of such killings in recent months.
Karzai ordered an investigation on Sunday into allegations that missiles from US helicopters struck civilians in eastern Afghanistan in an attack in Kunar, in Nuristan province, on Friday, which the defence ministry said killed or wounded 20 fighters.
Karzai ordered the defence and interior ministries, as well as local government officials, to investigate.
Karzai cited allegations by Tamim Nuristani, the governor of the province, that 15 civilians were killed and seven wounded during the attack.
"An independent commission should come," Nuristani told Al Jazeera. "Human rights lawyers and coalition force lawyers should investigate this ... And civilians should be heard in the investigation.
"A severe penalty should be given out to those who did this," he said.
Also on Sunday, a suicide bomber exploded a car bomb near a European Union Police Mission (Eupol) vehicle in northern Afghanistan, injuring seven people including three Germans, officials said.
The attack was outside the town of Kunduz in the north of the country, an area which has seen an increase in attacks.
Three German police officers and their Afghan interpreter were lightly wounded, Andrea Angeli, a Eupol spokesman said.
Mohammad Omar, the provincial governor, said three children were also hurt.
There was no immediate claim of responsibility.
Eupol's mission is to help build the Afghan police force and mentor interior ministry officials as part of international efforts to build the Afghan forces so they can bring security to the fractured country.
It consists of about 230 personnel mainly police, law enforcement and justice experts deployed in Kabul and some provinces.