At least 24 people including four policemen killed in southern province of Uruzgan.
Officials were keen to play down the fact Taliban fighters had breached the barriers of the Isaf base in Kunar province.
But the attack inflicted the worst losses US forces have suffered in Afghanistan in three years.
Four Afghan soldiers were also killed in the attack.
Between 400 and 500 fighters from various anti-government factions including Taliban, al-Qaeda and the Hezb-i-Islami faction were involved, a senior Afghan defence ministry official said on condition of anonymity.
Zabiullah Mujahid, a Taliban spokesman, cited the attack as evidence that the group, which was forced from power in Afghanistan by the US invasion in 2001, was growing stronger.
“The fighting in Afghanistan is getting heavier. When the Americans drop bombs on civilians ordinary people want revenge – that’s why they are joining the Taliban, strengthening us,” he told Al Jazeera.
“Now, instead of firing at the bases from far away, the Taliban has the ability to enter the bases and kill Americans.”
James Bays, Al Jazeera’s correspondent in Kabul, said: “The information we have is that this is a new base set that was set up by American forces … and because it was a new base, possibly it wasn’t as well fortified.
“We understand the Taliban started firing from the mountains, but it seems that this firing was a distraction and we are told by government sources that Taliban fighters managed to get very close to the base and then staged a surprise attack.
“Over 100 Taliban fighters attacked the base – some of them got on to the base for a time.”
Nato’s Laity told Al Jazeera the Taliban had taken over a village close to the base in order to carry out the attack.
“What they [the Taliban] did was they moved into an adjacent village – which was close to the combat outpost – they basically expelled the villagers and used their houses to attack us,” he said.
Earlier, Captain Mike Finney, a spokesperson for the Isaf, told Al Jazeera that while a number of US troops had indeed been killed, the “insurgents haven’t gained any ground”.
He said the attackers had failed in their goal to overrun the outpost which the Isaf soldiers had only recently occupied.
After the Isaf troops repulsed the Taliban fighters, an air raid was called.
An Afghan official confirmed the air raid and said there might also have been civilian casualties.
Meanwhile, in the southern province of Helmand, a roadside blast killed six Afghan private security guards escorting a supply convoy for Nato-led troops, an official said.
Mohammad Hussein Andiwal, the provincial police chief, said two other guards were wounded in the attack, which took place in Gereshk district.
In other news, the Taliban claimed responsibility on Monday for the abduction of an Afghan senator who was snatched at a gunpoint 70km from Kabul.
Abdul Wali, a member of the Upper House of the parliament from the province of Logar adjoining Kabul, was kidnapped on Sunday as he was driving with his two guards and driver, police said.
“Taliban have abducted Dr Abdul Wali and until now Taliban’s leading council have not made any decision on his fate,” Mujahid, the Taliban spokesman, told the AFP news agency.